Pyrazolecarboxylic acid derivatives and plant disease control agent

ABSTRACT

The present invention provides a plant disease control agent containing as active ingredient one or more compounds of the formula  1! 
     
         A--COOR.sup.1                                               1! 
    
     wherein 
     R 1  represents a hydrogen atom or a C 1  -C 4  alkyl group, and 
     A represents a group of the formula (A-1) or (A-2) ##STR1## R 2  represents a C 1  -C 4  alkyl group, R 3  represents a C 1  -C 4  alkyl group, 
     R 4  represents a halogen atom or a C 1  -C 4  alkyl group, and 
     R 5  represents a C 1  -C 4  alkyl group. 
     Further, the compound of A-1 in the formula  1! in which R 3  is a halogen atom is also included in the present invention.

FIELD OF THE INVENTION

The present invention relates to novel pyrazolecarboxylic acidderivatives, a plant disease control agent, especially, a paddy riceblast control agent, containing pyrazolecarboxylic acid derivatives orthiazolecarboxylic acid derivatives as an active ingredient.

TECHNICAL BACKGROUND

Some of 5-pyrazolecarboxylic acid derivatives have been already known asintermediates of medications and agricultural chemicals as described in,for example, Japanese Patent Application Laid-open No. Hei 2-292263,Japanese Patent Application Laid-open No. Hei 4-112873 and JapanesePatent Application Laid-open No. Hei 4-224565 and the literaturereferences indicated therein.

Some of 5-thiazolecarboxylic acid derivatives have been already known asintermediates of medications and agricultural chemicals as described in,for example, Japanese Patent Application Laid-open No. Hei 2-305073 andthe literature references indicated therein.

However, the above-mentioned laid-open publications and the literaturereferences do not at all describe a plant disease controlling activityof these compounds. Further, 5-pyrazolecarboxylic acid derivativescontaining a halogen atom in the 3-position are novel compoundsundescribed in the documents.

None of the existing agricultural and horticultural microbicides areunsatisfactory with respect to the problems such as an increase infungicide resistance and an environmental safety as well as an activityand a residual effect thereof. The development of less costly, usefulplant disease control agents have been desired.

DISCLOSURE OF THE INVENTION

Under these circumstances, the present inventors have conductedinvestigations to develop compounds having an excellent microbicidalactivity, and have consequently found that the compounds of thefollowing formulas 1! and 2! exhibit an excellent microbicidal activity.This finding has led to the completion of the present invention.

That is, the present invention relates to a plant disease control agentcontaining as an active ingredient a compound of the formula 1!:

    A--COOR.sup.1                                               1!

wherein

R¹ represents a hydrogen atom or a C₁ -C₄ alkyl group,

A represents a group of the formula (A-1) or (A-2) ##STR2## R²represents a C₁ -C₄ alkyl group, R³ represents a C₁ -C₄ alkyl group,

R⁴ represents a halogen atom or a C₁ -C₄ alkyl group, and

R⁵ represents a C₁ -C₄ alkyl group.

Some of the compounds of the formula 1! are known compounds.

Further, the present invention relates to a novel pyrazolecarboxylicacid derivative of the formula 2!: ##STR3## wherein X represents ahalogen atom,

R² represents a C¹ -C₄ alkyl group,

R⁶ represents a hydrogen atom, an alkali metal atom, an alkaline-earthmetal atom, ammonium, sulfonium, phosphonium, an optionally substitutedaryl group, an optionally substituted heteroaryl group, an optionallysubstituted heterocyclyl group, an optionally substituted aryl C₂ -C₄alkenyl group, -- C(R⁷)(R⁸)!_(m) --R⁹, --N(R¹⁰)(R¹¹) or --N═C(R¹²)(R¹³),

R⁷ and R⁸, independently from each other, represent a hydrogen atom, ahalogen atom, a C₁ -C₆ alkyl group (R⁷ and R⁸ may together form a cyclicalkyl group), a C₂ -C₆ alkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₆haloalkyl group, an optionally substituted aryl group, an optionallysubstituted heteroaryl group, a C₁ -C₄ alkylcarbonyl group, a C₁ -C₆alkoxycarbonyl group or a cyano group,

m is 0 or 1 to 5,

R⁹ represents a hydrogen atom, a halogen atom, a C₁ -C₁₀ alkyl group, aC₂ -C₁₀ alkenyl group, a C₂ -C₁₀ alkynyl group, a C₁ -C₁₀ haloalkylgroup, a C₂ -C₁₀ haloalkenyl group, a C₃ -C₁₀ cycloalkyl group, anoptionally substituted aryl group, an optionally substituted heteroarylgroup, an optionally substituted heterocyclyl group, a C₁ -C₆ alkoxygroup, a C₁ -C₆ haloalkoxy group, a C₂ -C₆ alkenyloxy group, a C₂ -C₆haloalkenyloxy group, a C₂ -C₆ alkynyloxy group, a C₃ -C₈ cycloalkyloxygroup, a C₁ -C₆ alkoxy C₁ -C₆ alkyl group, an optionally substitutedarylalkyloxy group, an optionally substituted aryloxy group, anoptionally substituted heteroaryloxy group, a cyano group, --C(O)--R¹⁴,--S(O)_(n) R¹⁵, --N(R¹⁶)(R¹⁷ ), --ON═C(R¹⁸)(R¹⁹) or OH,

R¹⁰ and R¹¹, independently from each other, represent a hydrogen atom, aC₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₂ -C₆ alkenyl group, aC₂ -C₆ haloalkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₄ alkoxy C₁ -C₄alkyl group, a C₁ -C₄ alkylthio C₁ -C₄ alkyl group, a C₁ -C₆alkylcarbonyl group, a C₁ -C₆ alkoxycarbonyl group, a C₁ -C₆alkylsulfonyl group, an optionally substituted aryl group, an optionallysubstituted arylcarbonyl group or an optionally substituted arylsulfonylgroup,

R¹² represents a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group or anoptionally substituted aryl group,

R¹³ represents an amino group, a C₁ -C₆ monoalkylamino group or a C₁ -C₅dialkylamino group,

R¹⁴ represents a hydrogen atom, OH, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, an optionally substituted aryl group, a C₁ -C₆ alkoxygroup, a C₁ -C₆ haloalkoxy group, a C₂ -C₆ alkenyloxy group, a C₂ -C₆haloalkenyloxy group, a C₂ -C₆ alkynyloxy group or an optionallysubstituted heterocyclyloxy group,

n is 0, 1 or 2,

R¹⁵ represents a hydrogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup or a C₂ -C₆ alkenyl group,

R¹⁶ and R¹⁷, independently from each other, represent a hydrogen atom, aC₁ -C₆ alkyl group (R¹⁶ and R¹⁷ may together form a cyclic alkyl group),a C₃ -C₆ cycloalkyl group, an optionally substituted aryl group, anoptionally substituted aryl C₂ -C₄ alkyl group, a C₁ -C₆ alkylcarbonylgroup, an optionally substituted arylcarbonyl group or a C₁ -C₆alkoxycarbonyl group,

R¹⁸ and R¹⁹, independently from each other, represent a hydrogen atom, aC₁ -C₆ alkyl group or an optionally substituted aryl group,

the expression "optionally substituted" means unsubstituted orsubstituted with 1 to 9 groups selected from a halogen atom, a cyanogroup, a nitro group, a C₁ -C₄ alkyl group, a C₁ -C₄ alkoxy group, a C₁-C₄ haloalkyl group, a C₁ -C₄ haloalkoxy group, an aryl group, anaryloxy group, a benzyl group, a benzyloxy group, a C₃ -C₆ cycloalkylgroup, a C₁ -C₄ alkoxycarbonyl group, a C₁ -C₄ alkylthio group, a C₁ -C₄alkylsulfinyl, a C₁ -C₄ alkylsulfonyl group, a styryl group, an aminogroup, a C₁ -C₄ alkoxycarbonylamino group, a C₁ -C₄ alkoxycarbonyloxygroup and/or an aminocarbonyl group,

the "aryl" group means a residue obtained by removing one hydrogen atombound to a carbon atom of an aromatic ring from an aromatic hydrocarboncompound,

the "heteroaryl" group means a residue obtained by removing one hydrogenatom bound to a carbon atom of a heterocyclic ring from a 5-membered or6-membered aromatic heterocyclic compound, and

the "heterocyclyl group" means a residue obtained by removing a hydrogenatom bound to a carbon atom of a heterocyclic ring from a 3- to6-membered non-aromatic heterocyclic compound; and to a plant diseasecontrol agent containing the above-mentioned derivative as an activeingredient.

In the compound of the formula 1!, A is a group of the formula A-1! orA-2!. Examples of the C₁ -C₄ alkyl group of R¹ to R⁵ include a methylgroup, an ethyl group, an n- or i-propyl group, and an n-, s-, i- ortert-butyl group. Examples of the halogen atom of R⁴ include a chlorineatom, a bromine atom, a fluorine atom and an iodine atom.

Preferably, R² and R³ are methyl groups, R⁴ is a chlorine atom or amethyl group, and R⁵ is a methyl group or an ethyl group.

In the compound of the formula 2!, it is a structural characteristicfeature of the compounds of the present invention that X is a halogenatom and R² is a C₁ -C₄ alkyl group. Examples of the halogen atominclude a chlorine atom, a bromine atom, a fluorine atom and an iodineatom. The chlorine atom or the bromine atom is especially preferable.Examples of the C₁ -C₄ alkyl group include a methyl group, an ethylgroup, an n- or i-propyl group and an n-, s-, i- or tert-butyl group.The methyl group is especially preferable.

R⁶ is not particularly limited. Especially, R⁶ represents -- C(R⁷)(R⁸)!_(m) --R⁹ in which R⁷ and R⁸ each represent a hydrogen atom, a methylgroup or an ethyl group, R⁹ represents a hydrogen atom, a C₁ -C₁₀ alkylgroup or an optionally substituted aryl group, and m is 0 to 2.Preferable examples thereof include a methyl group, an ethyl group, apropyl group, a butyl group, a phenyl group, a benzyl group, a2-phenylethyl group or a 2-phenylpropyl group.

The definitions for the substituents of R⁶ are as follows.

The halogen atom means a fluorine, chlorine, bromine or iodine atom.

Examples of the C₁ -C₄ alkyl group, the C₁ -C₆ alkyl group and the C₁-C₁₀ alkyl group include a methyl group, an ethyl group, an n- ori-propyl group, an n-, s-, i- or tert-butyl group, a pentyl group, ahexyl group, an octyl group, a nonyl group and an octyl group.

Examples of the aryl group include a phenyl group, a naphthyl group andan anthranyl group.

Examples of the heteroaryl group include a furyl group, a thienyl group,a pyrrolyl group, a pyrazolyl group, an imidazolyl group, a pyridylgroup, a pyrimidinyl group, a pyridazinyl group and a pyrazinyl group.

Examples of the heterocyclyl group include an oxiranyl group, anoxetanyl group, a tetrahydrofuryl group, a dioxolanyl group, atetrahydropyranyl group, a dioxanyl group, a thiiranyl group, atetrahydrothienyl group, a pyrrolidinyl group, a piperidyl group, apiperazinyl group, a morpholinylgroup and a thiomorpholinyl group.

The compounds of the present invention exhibits almost no or very weakantimicrobial activity against paddy rice blast microbes in experimentsusing laboratory dish. However, when the compounds are applied to apaddy either directly or on water surface, they exhibit an excellentactivity of controlling the paddy rice blast disease. That is, it isconsidered that the compounds of the present invention expediteproduction of antimicrobial products within the paddy rice and impartsresistance to the disease, thereby controlling infection of the paddyrice blast microbes and preventing the attack of the disease.

Among the above-mentioned plant disease control agents, especially paddyrice blast control agents in the present invention, preferable groupsare mentioned below.

(1) a plant disease control agent in which A is a group of the formula(A-1);

(2) a plant disease control agent in which A represents a group of theformula (A-1), R² represents a methyl group, and R³ represents a methylgroup;

(3) a plant disease control agent in which A represents a group of theformula (A-2); and

(4) a plant disease control agent in which A represents a group of theformula (A-2), R⁴ represents a chlorine atom or a methyl group, and R⁵represents a methyl group or an ethyl group.

Among the pyrazolecarboxylic acid derivatives of the formula 2! in thepresent invention, preferable groups are mentioned below.

(5) pyrazolecarboxylic acid derivatives of the formula in which Xrepresents a chlorine atom or a bromine atom, and R² represents a methylgroup;

(6) pyrazolecarboxylic acid derivatives of the formula in which Xrepresents a chlorine atom or a bromine atom, R² represents a methylgroup, and R⁶ represents -- C(R⁷)(R⁸)!_(m) --R⁹ group (wherein R⁷, R⁸,R⁹ and m have the same meanings as defined above);

(7) pyrazolecarboxylic acid derivatives of the formula in which Xrepresents a chlorine atom, R² represents a methyl group, R⁶ represents-- C(R⁷)(R⁸)!_(m) --R⁹ group (wherein R⁷ and R⁸, independently from eachother, represent a hydrogen atom, a methyl group or an ethyl group, R⁹represents a hydrogen atom, a C₁ -C₁₀ alkyl group or an optionallysubstituted aryl group, and m is 0, 1 or 2); and

(8) pyrazolecarboxylic acid derivatives of the formula in which Xrepresents a chlorine atom, R² represents a methyl group, and R⁶represents a methyl group, an ethyl group, a propyl group, a butylgroup, a phenyl group, a benzyl group, a 2-phenylethyl group or a2-phenylpropyl group.

A plant disease control agent, especially, a paddy rice blast controlagent containing as an active ingredient at least one of theabove-mentioned pyrazolecarboxylic acid derivatives of the formula 2!and the groups (5) to (8) thereof is also included in the presentinvention.

Examples of the active ingredient of the formula 1! in the plant diseasecontrol agent of the present invention are shown in Tables 1 and 2.

However, the compounds of the present invention are not limited thereto.

In these tables, Me indicates a methyl group, Et indicates an ethylgroup, Pr indicates a propyl group, Bu indicates a butyl group, iindicates iso, s indicates secondary, and t indicates tertiary.

                  TABLE 1                                                         ______________________________________                                         ##STR4##                                                                     Compound No.    R.sup.3   R.sup.2  R.sup.1                                    ______________________________________                                        1.1             Me        Me       H                                          1.2             Me        Me       Me                                         1.3             Me        Me       Et                                         1.4             Me        Me       Pr                                         1.5             Me        Me       i-Pr                                       1.6             Me        Me       Bu                                         1.7             Me        Me       s-Bu                                       1.8             Me        Me       t-Bu                                       1.9             Et        Me       H                                          1.10            Et        Me       Me                                         1.11            Et        Me       Et                                         1.12            Pr        Me       H                                          1.13            Pr        Me       Me                                         1.14            Pr        Me       Et                                         1.15            Bu        Me       H                                          1.16            Bu        Me       Me                                         1.17            Bu        Me       Et                                         1.18            Me        Et       H                                          1.19            Me        Et       Me                                         1.20            Me        Et       Et                                         1.21            Me        Pr       H                                          1.22            Me        Pr       Me                                         1.23            Me        Pr       Et                                         1.24            Me        Bu       H                                          1.25            Me        Bu       Me                                         1.26            Me        Bu       Et                                         ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                         ##STR5##                                                                     Compound No.    R.sup.4   R.sup.5  R.sup.1                                    ______________________________________                                        2.1             Me        Me       H                                          2.2             Me        Me       Me                                         2.3             Me        Me       Et                                         2.4             Me        Me       Pr                                         2.5             Me        Me       i-Pr                                       2.6             Me        Me       Bu                                         2.7             Me        Me       s-Bu                                       2.8             Me        Me       t-Bu                                       2.9             Et        Me       H                                          2.10            Et        Me       Me                                         2.11            Et        Me       Et                                         2.12            Pr        Me       H                                          2.13            Pr        Me       Me                                         2.14            Pr        Me       Et                                         2.15            Bu        Me       H                                          2.16            Bu        Me       Me                                         2.17            Bu        Me       Et                                         2.18            Me        Et       H                                          2.19            Me        Et       Me                                         2.20            Me        Et       Et                                         2.21            Me        Et       Pr                                         2.22            Me        Et       i-Pr                                       2.23            Me        Et       Bu                                         2.24            Me        Et       s-Bu                                       2.25            Me        Et       t-Bu                                       2.26            Me        Pr       H                                          2.27            Me        Pr       Me                                         2.28            Me        Pr       Et                                         2.29            Me        Bu       H                                          2.30            Me        Bu       Me                                         2.31            Me        Bu       Et                                         2.32            Cl        Me       H                                          2.33            Cl        Me       Me                                         2.34            Cl        Me       Et                                         2.35            Cl        Me       Pr                                         2.36            Cl        Me       i-Pr                                       2.37            Cl        Me       Bu                                         2.38            Cl        Me       s-Bu                                       2.39            Cl        Me       t-Bu                                       2.40            Cl        Et       H                                          2.41            Cl        Et       Me                                         2.42            Cl        Et       Et                                         2.43            Cl        Pr       H                                          2.44            Cl        Bu       H                                          2.45            Br        Me       H                                          2.46            Br        Me       Me                                         2.47            Br        Me       Et                                         2.48            F         Me       H                                          ______________________________________                                    

Next, the compounds of the present invention of the formula 2! are shownin Tables 3 to 6.

However, the compounds of the present invention are not to be limitedthereto.

In the tables, Me indicates a methyl group, Et does an ethyl group, Prdoes a propyl group, Bu does a butyl group, Pen does a pentyl group, Hexdoes a hexyl group, Ph does a phenyl group, i does iso, s- doessecondary, t- does tertiary, and cyc- does cyclo.

                  TABLE 3                                                         ______________________________________                                        In the compounds of                                                            ##STR6##                                                                      ##STR7##                                                                      ##STR8##                                                                      ##STR9##                                                                      ##STR10##                                                                     ##STR11##                                                                    or                                                                             ##STR12##                                                                    Compound No. B             D                                                  ______________________________________                                        3.1          H                                                                3.2          2-Me                                                             3.3          3-Me                                                             3.4          4-Me                                                             3.5          2-Et                                                             3.6          3-Et                                                             3.7          4-Et                                                             3.8          2-Pr                                                             3.9          3-Pr                                                             3.10         4-Pr                                                             3.11         2-i-Pr                                                           3.12         3-i-Pr                                                           3.13         4-i-Pr                                                           3.14         2-t-Bu                                                           3.15         3-t-Bu                                                           3.16         4-t-Bu                                                           3.17         2,4-Me.sub.2                                                     3.18         2,5-Me.sub.2                                                     3.19         2,6-Me.sub.2                                                     3.20         3,4-Me.sub.2                                                     3.21         2,4,6-Me.sub.3                                                   3.22         4-t-Bu-2,6-Me.sub.2                                              3.23         3,5-(t-Bu).sub.2 -4-OH                                           3.24         2-CF.sub.3                                                       3.25         3-CF.sub.3                                                       3.26         4-CF.sub.3                                                       3.27         2-Cl                                                             3.28         3-Cl                                                             3.29         4-Cl                                                             3.30         2,4-Cl.sub.2                                                     3.31         2,5-Cl.sub.2                                                     3.32         2,6-Cl.sub.2                                                     3.33         3,4-Cl.sub.2                                                     3.34         2,4,6-Cl.sub.3                                                   3.35         2-F                                                              3.36         3-F                                                              3.37         4-F                                                              3.38         2,4-F.sub.2                                                      3.39         3,4-F.sub.2                                                      3.40         2,6-F.sub.2                                                      3.41         2-Cl-6-F                                                         3.42         2-Br                                                             3.43         3-Br                                                             3.44         4-Br                                                             3.45         2,4-Br.sub.2                                                     3.46         2,6-Br.sub.2                                                     3.47         3,4-Br.sub.2                                                     3.48         4-I                                                              3.49         4-Cl-2-Me                                                        3.50         2-NO.sub.2                                                       3.51         3-NO.sub.2                                                       3.52         4-NO.sub.2                                                       3.53         2-Cl-4-NO.sub.2                                                  3.54         3-Cl-4-NO.sub.2                                                  3.55         4-Cl-3-NO.sub.2                                                  3.56         4-OH                                                             3.57         2-OMe                                                            3.58         3-OMe                                                            3.59         4-OMe                                                            3.60         4-OBu                                                            3.61         3,4-(OMe).sub.2                                                  3.62         4-SMe                                                            3.63         4-SOMe                                                           3.64         4-SO.sub.2 Me                                                    3.65         4-OCHF.sub.2                                                     3.66         4-OCF.sub.3                                                      3.67         2-Ph                                                             3.68         3-Ph                                                             3.69         4-Ph                                                             3.70         2-OPh                                                            3.71         3-OPh                                                            3.72         4-OPh                                                            3.73         2-OCH.sub.2 Ph                                                   3.74         3-OCH.sub.2 Ph                                                   3.75         4-OCH.sub.2 Ph                                                   3.76         4-CHCHPh                                                         3.77         4-NH.sub.2                                                       3.78         4-NMe.sub.2                                                      3.79         4-OCO.sub.2 Me                                                   3.80         4-OCO.sub.2 Et                                                   3.81         4-OCO.sub.2 t-Bu                                                 3.82         3-Cl-4-OCO.sub.2 t-Bu                                            3.83         4-NHCO.sub.2 Me                                                  3.84         4-NHCO.sub.2 Et                                                  3.85         4-NHCO.sub.2 t-Bu                                                3.86         4-CO.sub.2 Me                                                    3.87         4-CO.sub.2 Et                                                    3.88         4-CONHMe                                                         3.89         4-CONHEt                                                         3.90         4-CONMe.sub.2                                                    3.91         4-CONEt.sub.2                                                    3.92         4-CN                                                             3.93         H             CH.sub.2                                           3.94         2-Me          CH.sub.2                                           3.95         3-Me          CH.sub.2                                           3.96         4-Me          CH.sub.2                                           3.97         2-Et          CH.sub.2                                           3.98         3-Et          CH.sub.2                                           3.99         4-Et          CH.sub.2                                           3.100        2-Pr          CH.sub.2                                           3.101        3-Pr          CH.sub.2                                           3.102        4-Pr          CH.sub.2                                           3.103        2-i-Pr        CH.sub.2                                           3.104        3-i-Pr        CH.sub.2                                           3.105        4-i-Pr        CH.sub.2                                           3.106        2-t-Bu        CH.sub.2                                           3.107        3-t-Bu        CH.sub.2                                           3.108        4-t-Bu        CH.sub.2                                           3.109        2,4-Me.sub.2  CH.sub.2                                           3.110        2,5-Me.sub.2  CH.sub.2                                           3.111        2,6-Me.sub.2  CH.sub.2                                           3.112        3,4-Me.sub.2  CH.sub.2                                           3.113        2,4,6-Me.sub.3                                                                              CH.sub.2                                           3.114        4-t-Bu-2,6-Me.sub.2                                                                         CH.sub.2                                           3.115        3,5-(t-Bu).sub.2 -4-OH                                                                      CH.sub.2                                           3.116        2-CF.sub.3    CH.sub.2                                           3.117        3-CF.sub.3    CH.sub.2                                           3.118        4-CF.sub.3    CH.sub.2                                           3.119        2-Cl          CH.sub.2                                           3.120        3-Cl          CH.sub.2                                           3.121        4-Cl          CH.sub.2                                           3.122        2,4-Cl.sub.2  CH.sub.2                                           3.123        2,5-Cl.sub.2  CH.sub.2                                           3.124        2,6-Cl.sub.2  CH.sub.2                                           3.125        3,4-Cl.sub.2  CH.sub.2                                           3.126        2,4,6-Cl.sub.3                                                                              CH.sub.2                                           3.127        2-F           CH.sub.2                                           3.128        3-F           CH.sub.2                                           3.129        4-F           CH.sub.2                                           3.130        2,4-F.sub.2   CH.sub.2                                           3.131        3,4-F.sub.2   CH.sub.2                                           3.132        2,6-F.sub.2   CH.sub.2                                           3.133        2-Cl-6-F      CH.sub.2                                           3.134        2-Br          CH.sub.2                                           3.135        3-Br          CH.sub.2                                           3.136        4-Br          CH.sub.2                                           3.137        2,4-Br.sub.2  CH.sub.2                                           3.138        2,6-Br.sub.2  CH.sub.2                                           3.139        3,4-Br.sub.2  CH.sub.2                                           3.140        4-I           CH.sub.2                                           3.141        4-Cl-2-Me     CH.sub.2                                           3.142        2-NO.sub.2    CH.sub.2                                           3.143        3-NO.sub.2    CH.sub.2                                           3.144        4-NO.sub.2    CH.sub.2                                           3.145        2-Cl-4-NO.sub.2                                                                             CH.sub.2                                           3.146        3-Cl-4-NO.sub.2                                                                             CH.sub.2                                           3.147        4-Cl-3-NO.sub.2                                                                             CH.sub.2                                           3.148        4-OH          CH.sub.2                                           3.149        2-OMe         CH.sub.2                                           3.150        3-OMe         CH.sub.2                                           3.151        4-OMe         CH.sub.2                                           3.152        4-OBu         CH.sub.2                                           3.153        3,4-(OMe).sub.2                                                                             CH.sub.2                                           3.154        4-SMe         CH.sub.2                                           3.155        4-SOMe        CH.sub.2                                           3.156        4-SO.sub.2 Me CH.sub.2                                           3.157        4-OCHF.sub.2  CH.sub.2                                           3.158        4-OCF.sub.3   CH.sub.2                                           3.159        2-Ph          CH.sub.2                                           3.160        3-Ph          CH.sub.2                                           3.161        4-Ph          CH.sub.2                                           3.162        2-OPh         CH.sub.2                                           3.163        3-OPh         CH.sub.2                                           3.164        4-OPh         CH.sub.2                                           3.165        2-OCH.sub.2 Ph                                                                              CH.sub.2                                           3.166        3-OCH.sub.2 Ph                                                                              CH.sub.2                                           3.167        4-OCH.sub.2 Ph                                                                              CH.sub.2                                           3.168        4-CHCHPh      CH.sub.2                                           3.169        4-NH.sub.2    CH.sub.2                                           3.170        4-NMe.sub.2   CH.sub.2                                           3.171        4-OCO.sub.2 Me                                                                              CH.sub.2                                           3.172        4-OCO.sub.2 Et                                                                              CH.sub.2                                           3.173        4-OCO.sub.2 t-Bu                                                                            CH.sub.2                                           3.174        3-Cl-4-OCO.sub.2 t-Bu                                                                       CH.sub.2                                           3.175        4-NHCO.sub.2 Me                                                                             CH.sub.2                                           3.176        4-NHCO.sub.2 Et                                                                             CH.sub.2                                           3.177        4-NHCO.sub.2 t-Bu                                                                           CH.sub.2                                           3.178        4-CO.sub.2 Me CH.sub.2                                           3.179        4-CO.sub.2 Et CH.sub.2                                           3.180        4-CONHMe      CH.sub.2                                           3.181        4-CONHEt      CH.sub.2                                           3.182        4-CONMe.sub.2 CH.sub.2                                           3.183        4-CONEt.sub.2 CH.sub.2                                           3.184        4-CN          CH.sub.2                                           3.185        H             (CH.sub.2).sub.2                                   3.186        2-Me          (CH.sub.2).sub.2                                   3.187        3-Me          (CH.sub.2).sub.2                                   3.188        4-Me          (CH.sub.2).sub.2                                   3.189        4-Et          (CH.sub.2).sub.2                                   3.190        4-i-Pr        (CH.sub.2).sub.2                                   3.191        4-t-Bu        (CH.sub.2).sub.2                                   3.192        2,4-Me.sub.2  (CH.sub.2).sub.2                                   3.193        2,6-Me.sub.2  (CH.sub.2).sub.2                                   3.194        3,4-Me.sub.2  (CH.sub.2).sub.2                                   3.195        4-CF.sub.3    (CH.sub.2).sub.2                                   3.196        2-Cl          (CH.sub.2).sub.2                                   3.197        3-Cl          (CH.sub.2).sub.2                                   3.198        4-Cl          (CH.sub.2).sub.2                                   3.199        2,4-Cl.sub.2  (CH.sub.2).sub.2                                   3.200        2,6-Cl.sub.2  (CH.sub.2).sub.2                                   3.201        2-F           (CH.sub.2).sub.2                                   3.202        3-F           (CH.sub.2).sub.2                                   3.203        4-F           (CH.sub.2).sub.2                                   3.204        2,4-F.sub.2   (CH.sub.2).sub.2                                   3.205        2,6-F.sub.2   (CH.sub.2).sub.2                                   3.206        4-Br          (CH.sub.2).sub.2                                   3.207        2,4-Br.sub.2  (CH.sub.2).sub.2                                   3.208        4-I           (CH.sub.2).sub.2                                   3.209        4-NO.sub.2    (CH.sub.2).sub.2                                   3.210        4-OMe         (CH.sub.2).sub.2                                   3.211        3,4-(OMe).sub.2                                                                             (CH.sub.2).sub.2                                   3.212        4-SMe         (CH.sub.2).sub.2                                   3.213        4-SO.sub.2 Me (CH.sub.2).sub.2                                   3.214        4-OCHF.sub.2  (CH.sub.2).sub.2                                   3.215        4-OCF.sub.3   (CH.sub.2).sub.2                                   3.216        4-Ph          (CH.sub.2).sub.2                                   3.217        2-OPh         (CH.sub.2).sub.2                                   3.218        3-OPh         (CH.sub.2).sub.2                                   3.219        4-OPh         (CH.sub.2).sub.2                                   3.220        2-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2                                   3.221        3-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2                                   3.222        4-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2                                   3.223        4-CHCHPh      (CH.sub.2).sub.2                                   3.224        4-NH.sub.2    (CH.sub.2).sub.2                                   3.225        4-OCO.sub.2 Et                                                                              (CH.sub.2).sub.2                                   3.226        4-NHCO.sub.2 Et                                                                             (CH.sub.2).sub.2                                   3.227        4-CO.sub.2 Et (CH.sub.2).sub.2                                   3.228        4-CONMe.sub.2 (CH.sub.2).sub.2                                   3.229        H             CHMe                                               3.230        2-Me          CHMe                                               3.231        3-Me          CHMe                                               3.232        4-Me          CHMe                                               3.233        4-Et          CHMe                                               3.234        4-i-Pr        CHMe                                               3.235        4-t-Bu        CHMe                                               3.236        2,4-Me.sub.2  CHMe                                               3.237        2,6-Me.sub.2  CHMe                                               3.238        3,4-Me.sub.2  CHMe                                               3.239        4-CF.sub.3    CHMe                                               3.240        2-Cl          CHMe                                               3.241        3-Cl          CHMe                                               3.242        4-Cl          CHMe                                               3.243        2,4-Cl.sub.2  CHMe                                               3.244        2,6-Cl.sub.2  CHMe                                               3.245        2-F           CHMe                                               3.246        3-F           CHMe                                               3.247        4-F           CHMe                                               3.248        2,4-F.sub.2   CHMe                                               3.249        2,6-F.sub.2   CHMe                                               3.250        4-Br          CHMe                                               3.251        2,4-Br.sub.2  CHMe                                               3.252        4-I           CHMe                                               3.253        4-NO.sub.2    CHMe                                               3.254        4-OMe         CHMe                                               3.255        3,4-(OMe).sub.2                                                                             CHMe                                               3.256        4-SMe         CHMe                                               3.257        4-SO.sub.2 Me CHMe                                               3.258        4-OCHF.sub.2  CHMe                                               3.259        4-OCF.sub.3   CHMe                                               3.260        4-Ph          CHMe                                               3.261        2-OPh         CHMe                                               3.262        3-OPh         CHMe                                               3.263        4-OPh         CHMe                                               3.264        2-OCH.sub.2 Ph                                                                              CHMe                                               3.265        3-OCH.sub.2 Ph                                                                              CHMe                                               3.266        4-OCH.sub.2 Ph                                                                              CHMe                                               3.267        4-CHCHPh      CHMe                                               3.268        4-NH.sub.2    CHMe                                               3.269        4-OCO.sub.2 Et                                                                              CHMe                                               3.270        4-NHCO.sub.2 Et                                                                             CHMe                                               3.271        4-CO.sub.2 Et CHMe                                               3.272        4-CONMe.sub.2 CHMe                                               3.273        H             (CH.sub.2).sub.3                                   3.274        2-Me          (CH.sub.2).sub.3                                   3.275        3-Me          (CH.sub.2).sub.3                                   3.276        4-Me          (CH.sub.2).sub.3                                   3.277        4-Et          (CH.sub.2).sub.3                                   3.278        4-i-Pr        (CH.sub.2).sub.3                                   3.279        4-t-Bu        (CH.sub.2).sub.3                                   3.280        2,4-Me.sub.2  (CH.sub.2).sub.3                                   3.281        2,6-Me.sub.2  (CH.sub.2).sub.3                                   3.282        3,4-Me.sub.2  (CH.sub.2).sub.3                                   3.283        4-CF.sub.3    (CH.sub.2).sub.3                                   3.284        2-Cl          (CH.sub.2).sub.3                                   3.285        3-Cl          (CH.sub.2).sub.3                                   3.286        4-Cl          (CH.sub.2).sub.3                                   3.287        2,4-Cl.sub.2  (CH.sub.2).sub.3                                   3.288        2,6-Cl.sub.2  (CH.sub.2).sub.3                                   3.289        2-F           (CH.sub.2).sub.3                                   3.290        3-F           (CH.sub.2).sub.3                                   3.291        4-F           (CH.sub.2).sub.3                                   3.292        2,4-F.sub.2   (CH.sub.2).sub.3                                   3.293        2,6-F.sub.2   (CH.sub.2).sub.3                                   3.294        4-Br          (CH.sub.2).sub.3                                   3.295        2,4-Br.sub.2  (CH.sub.2).sub.3                                   3.296        4-I           (CH.sub.2).sub.3                                   3.297        4-NO.sub.2    (CH.sub.2).sub.3                                   3.298        4-OMe         (CH.sub.2).sub.3                                   3.299        3,4-(OMe).sub.2                                                                             (CH.sub.2).sub.3                                   3.300        4-SMe         (CH.sub.2).sub.3                                   3.301        4-SO.sub.2 Me (CH.sub.2).sub.3                                   3.302        4-OCHF.sub.2  (CH.sub.2).sub.3                                   3.303        4-OCF.sub.2   (CH.sub.2).sub.3                                   3.304        4-Ph          (CH.sub.2).sub.3                                   3.305        2-OPh         (CH.sub.2).sub.3                                   3.306        3-OPh         (CH.sub.2).sub.3                                   3.307        4-OPh         (CH.sub.2).sub.3                                   3.308        2-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3                                   3.309        3-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3                                   3.310        4-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3                                   3.311        4-CHCHPh      (CH.sub.2).sub.3                                   3.312        4-NH.sub.2    (CH.sub.2).sub.3                                   3.313        4-OCO.sub.2 Et                                                                              (CH.sub.2).sub.3                                   3.314        4-NHCO.sub.2 Et                                                                             (CH.sub.2).sub.3                                   3.315        4-CO.sub.2 Et (CH.sub.2).sub.3                                   3.316        4-CONMe.sub.2 (CH.sub.2).sub.3                                   3.317        H             CH.sub.2 CHMe                                      3.318        2-Me          CH.sub.2 CHMe                                      3.319        4-Me          CH.sub.2 CHMe                                      3.320        4-Et          CH.sub.2 CHMe                                      3.321        4-t-Bu        CH.sub.2 CHMe                                      3.322        2,4-Me.sub.2  CH.sub.2 CHMe                                      3.323        2,6-Me.sub.2  CH.sub.2 CHMe                                      3.324        3,4-Me.sub.2  CH.sub.2 CHMe                                      3.325        4-CF.sub.3    CH.sub.2 CHMe                                      3.326        2-Cl          CH.sub.2 CHMe                                      3.327        4-Cl          CH.sub.2 CHMe                                      3.328        2,4-Cl.sub.2  CH.sub.2 CHMe                                      3.329        2,6-Cl.sub.2  CH.sub.2 CHMe                                      3.330        2-F           CH.sub.2 CHMe                                      3.331        4-F           CH.sub.2 CHMe                                      3.332        2,4-F.sub.2   CH.sub.2 CHMe                                      3.333        2,6-F.sub.2   CH.sub.2 CHMe                                      3.334        4-Br          CH.sub.2 CHMe                                      3.335        4-NO.sub.2    CH.sub.2 CHMe                                      3.336        4-OMe         CH.sub.2 CHMe                                      3.337        4-SMe         CH.sub.2 CHMe                                      3.338        4-SO.sub.2 Me CH.sub.2 CHMe                                      3.339        4-OCHF.sub.2  CH.sub.2 CHMe                                      3.340        4-OCF.sub.3   CH.sub.2 CHMe                                      3.341        4-Ph          CH.sub.2 CHMe                                      3.342        4-OPh         CH.sub.2 CHMe                                      3.343        4-OCH.sub.2 Ph                                                                              CH.sub.2 CHMe                                      3.344        4-CHCHPh      CH.sub.2 CHMe                                      3.345        4-NH.sub.2    CH.sub.2 CHMe                                      3.346        4-OCO.sub.2 Et                                                                              CH.sub.2 CHMe                                      3.347        4-NHCO.sub.2 Et                                                                             CH.sub.2 CHMe                                      3.348        4-CO.sub.2 Et CH.sub.2 CHMe                                      3.349        4-CONMe.sub.2 CH.sub.2 CHMe                                      3.350        H             CH(Me)CH.sub.2                                     3.351        2-Me          CH(Me)CH.sub.2                                     3.352        4-Me          CH(Me)CH.sub.2                                     3.353        4-Et          CH(Me)CH.sub.2                                     3.354        4-t-Bu        CH(Me)CH.sub.2                                     3.355        2,4-Me.sub.2  CH(Me)CH.sub.2                                     3.356        2,6-Me.sub.2  CH(Me)CH.sub.2                                     3.357        3,4-Me.sub.2  CH(Me)CH.sub.2                                     3.358        4-CF.sub.3    CH(Me)CH.sub.2                                     3.359        2-Cl          CH(Me)CH.sub.2                                     3.360        4-Cl          CH(Me)CH.sub.2                                     3.361        2,4-Cl.sub.2  CH(Me)CH.sub.2                                     3.362        2,6-Cl.sub.2  CH(Me)CH.sub.2                                     3.363        2-F           CH(Me)CH.sub.2                                     3.364        4-F           CH(Me)CH.sub.2                                     3.365        2,4-F.sub.2   CH(Me)CH.sub.2                                     3.366        2,6-F.sub.2   CH(Me)CH.sub.2                                     3.367        4-Br          CH(Me)CH.sub.2                                     3.368        4-NO.sub.2    CH(Me)CH.sub.2                                     3.369        4-OMe         CH(Me)CH.sub.2                                     3.370        4-SMe         CH(Me)CH.sub.2                                     3.371        4-SO.sub.2 Me CH(Me)CH.sub.2                                     3.372        4-OCHF.sub.2  CH(Me)CH.sub.2                                     3.373        4-OCF.sub.3   CH(Me)CH.sub.2                                     3.374        4-Ph          CH(Me)CH.sub.2                                     3.375        4-OPh         CH(Me)CH.sub.2                                     3.376        4-OCh.sub.2 Ph                                                                              CH(Me)CH.sub.2                                     3.377        4-CHCHPh      CH(Me)CH.sub.2                                     3.378        4-NH.sub.2    CH(Me)CH.sub.2                                     3.379        4-OCO.sub.2 Et                                                                              CH(Me)CH.sub.2                                     3.380        4-NHCO.sub.2 Et                                                                             CH(Me)CH.sub.2                                     3.381        4-CO.sub.2 Et CH(Me)CH.sub.2                                     3.382        4-CONMe.sub.2 CH(Me)CH.sub.2                                     3.383        H             (CH.sub.2).sub.4                                   3.384        2-Me          (CH.sub.2).sub.4                                   3.385        4-Me          (CH.sub.2).sub.4                                   3.386        4-Et          (CH.sub.2).sub.4                                   3.387        4-t-Bu        (CH.sub.2).sub.4                                   3.388        2,4-Me.sub.2  (CH.sub.2).sub.4                                   3.389        2,6-Me.sub.2  (CH.sub.2).sub.4                                   3.390        3,4-Me.sub.2  (CH.sub.2).sub.4                                   3.391        4-CF.sub.3    (CH.sub.2).sub.4                                   3.392        2-Cl          (CH.sub.2).sub.4                                   3.393        4-Cl          (CH.sub.2).sub.4                                   3.394        2,4-Cl.sub.2  (CH.sub.2).sub.4                                   3.395        2,6-Cl.sub.2  (CH.sub.2).sub.4                                   3.396        2-F           (CH.sub.2).sub.4                                   3.397        4-F           (CH.sub.2).sub.4                                   3.398        2,4-F.sub.2   (CH.sub.2).sub.4                                   3.399        2,6-F.sub.2   (CH.sub.2).sub.4                                   3.400        4-Br          (CH.sub.2).sub.4                                   3.401        4-NO.sub.2    (CH.sub.2).sub.4                                   3.402        4-OMe         (CH.sub.2).sub.4                                   3.403        4-SMe         (CH.sub.2).sub.4                                   3.404        4-SO.sub.2 Me (CH.sub.2).sub.4                                   3.405        4-OCHF.sub.2  (CH.sub.2).sub.4                                   3.406        4-OCF.sub.3   (CH.sub.2).sub.4                                   3.407        4-Ph          (CH.sub.2).sub.4                                   3.408        4-OPh         (CH.sub.2).sub.4                                   3.409        4-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.4                                   3.410        4-CHCHPh      (CH.sub.2).sub.4                                   3.411        4-NH.sub.2    (CH.sub.2).sub.4                                   3.412        4-OCO.sub.2 Et                                                                              (CH.sub.2).sub.4                                   3.413        4-NHCO.sub.2 Et                                                                             (CH.sub.2).sub.4                                   3.414        4-CO.sub.2 Et (CH.sub.2).sub.4                                   3.415        4-CONMe.sub.2 (CH.sub.2).sub.4                                   3.416        H             CH(Me)CH(Me)                                       3.417        2-Me          CH(Me)CH(Me)                                       3.418        4-Me          CH(Me)CH(Me)                                       3.419        4-Et          CH(Me)CH(Me)                                       3.420        4-t-Bu        CH(Me)CH(Me)                                       3.421        2,4-Me.sub.2  CH(Me)CH(Me)                                       3.422        2,6-Me.sub.2  CH(Me)CH(Me)                                       3.423        3,4-Me.sub.2  CH(Me)CH(Me)                                       3.424        4-CF.sub.3    CH(Me)CH(Me)                                       3.425        2-Cl          CH(Me)CH(Me)                                       3.426        4-Cl          CH(Me)CH(Me)                                       3.427        2,4-Cl.sub.2  CH(Me)CH(Me)                                       3.428        2,6-Cl.sub.2  CH(Me)CH(Me)                                       3.429        2-F           CH(Me)CH(Me)                                       3.430        4-F           CH(Me)CH(Me)                                       3.431        2,4-F.sub.2   CH(Me)CH(Me)                                       3.432        2,6-F.sub.2   CH(Me)CH(Me)                                       3.433        4-Br          CH(Me)CH(Me)                                       3.434        4-NO.sub.2    CH(Me)CH(Me)                                       3.435        4-OMe         CH(Me)CH(Me)                                       3.436        4-SMe         CH(Me)CH(Me)                                       3.437        4-SO.sub.2 Me CH(Me)CH(Me)                                       3.438        4-OCHF.sub.2  CH(Me)CH(Me)                                       3.439        4-OCF.sub.3   CH(Me)CH(Me)                                       3.440        4-Ph          CH(Me)CH(Me)                                       3.441        4-OPh         CH(Me)CH(Me)                                       3.442        4-OCH.sub.2 Ph                                                                              CH(Me)CH(Me)                                       3.443        4-CHCHPh      CH(Me)CH(Me)                                       3.444        4-NH.sub.2    CH(Me)CH(Me)                                       3.445        4-OCO.sub.2 Et                                                                              CH(Me)CH(Me)                                       3.446        4-NHCO.sub.2 Et                                                                             CH(Me)CH(Me)                                       3.447        4-CO.sub.2 Et CH(Me)CH(Me)                                       3.448        4-CONMe.sub.2 CH(Me)CH(Me)                                       3.449        H             CH.sub.2 C(Me).sub.2                               3.450        2-Me          CH.sub.2 C(Me).sub.2                               3.451        4-Me          CH.sub.2 C(Me).sub.2                               3.452        4-Et          CH.sub.2 C(Me).sub.2                               3.453        4-t-Bu        CH.sub.2 C(Me).sub.2                               3.454        2,4-Me.sub.2  CH.sub.2 C(Me).sub.2                               3.455        2,6-Me.sub.2  CH.sub.2 C(Me).sub.2                               3.456        3,4-Me.sub.2  CH.sub.2 C(Me).sub.2                               3.457        4-CF.sub.3    CH.sub.2 C(Me).sub.2                               3.458        2-Cl          CH.sub.2 C(Me).sub.2                               3.459        4-Cl          CH.sub.2 C(Me).sub.2                               3.460        2,4-Cl.sub.2  CH.sub.2 C(Me).sub.2                               3.461        2,6-Cl.sub.2  CH.sub.2 C(Me).sub.2                               3.462        2-F           CH.sub.2 C(Me).sub.2                               3.463        4-F           CH.sub.2 C(Me).sub.2                               3.464        2,4-F.sub.2   CH.sub.2 C(Me).sub.2                               3.465        2,6-F.sub.2   CH.sub.2 C(Me).sub.2                               3.466        4-Br          CH.sub.2 C(Me).sub.2                               3.467        4-NO.sub.2    CH.sub.2 C(Me).sub.2                               3.468        4-OMe         CH.sub.2 C(Me).sub.2                               3.469        4-SMe         CH.sub.2 C(Me).sub.2                               3.470        4-SO.sub.2 Me CH.sub.2 C(Me).sub.2                               3.471        4-OCHF.sub.2  CH.sub.2 C(Me).sub.2                               3.472        4-OCF.sub.3   CH.sub.2 C(Me).sub.2                               3.473        4-Ph          CH.sub.2 C(Me).sub.2                               3.474        4-OPh         CH.sub.2 C(Me).sub.2                               3.475        4-OCH.sub.2 Ph                                                                              CH.sub.2 C(Me).sub.2                               3.476        4-CHCHPh      CH.sub.2 C(Me).sub.2                               3.477        4-NH.sub.2    CH.sub.2 C(Me).sub.2                               3.478        4-OCO.sub.2 Et                                                                              CH.sub.2 C(Me).sub.2                               3.479        4-NHCO.sub.2 Et                                                                             CH.sub.2 C(Me).sub.2                               3.480        4-CO.sub.2 Et CH.sub.2 C(Me).sub.2                               3.481        4-CONMe.sub.2 CH.sub.2 C(Me).sub.2                               3.482        H             CH.sub.2 C(Me).sub.2 CH.sub.2                      3.483        2-Me          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.484        4-Me          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.485        4-Et          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.486        4-t-Bu        CH.sub.2 C(Me).sub.2 CH.sub.2                      3.487        2,4-Me.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.488        2,6-Me.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.489        3,4-Me.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.490        4-CF.sub.3    CH.sub.2 C(Me).sub.2 CH.sub.2                      3.491        2-Cl          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.492        4-Cl          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.493        2,4-Cl.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.494        2,6-Cl.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.495        2-F           CH.sub.2 C(Me).sub.2 CH.sub.2                      3.496        4-F           CH.sub.2 C(Me).sub.2 CH.sub.2                      3.497        2,4-F.sub.2   CH.sub.2 C(Me).sub.2 CH.sub.2                      3.498        2,6-F.sub.2   CH.sub.2 C(Me).sub.2 CH.sub.2                      3.499        4-Br          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.500        4-NO.sub.2    CH.sub.2 C(Me).sub.2 CH.sub.2                      3.501        4-OMe         CH.sub.2 C(Me).sub.2 CH.sub.2                      3.502        4-SMe         CH.sub.2 C(Me).sub.2 CH.sub.2                      3.503        4-SO.sub.2 Me CH.sub.2 C(Me).sub.2 CH.sub.2                      3.504        4-OCHF.sub.2  CH.sub.2 C(Me).sub.2 CH.sub.2                      3.505        4-OCF.sub.3   CH.sub.2 C(Me).sub.2 CH.sub.2                      3.506        4-Ph          CH.sub.2 C(Me).sub.2 CH.sub.2                      3.507        4-OPh         CH.sub.2 C(Me).sub.2 CH.sub.2                      3.508        4-OCH.sub.2 Ph                                                                              CH.sub.2 C(Me).sub.2 CH.sub.2                      3.509        4-CHCHPh      CH.sub.2 C(Me).sub.2 CH.sub.2                      3.510        4-NH.sub.2    CH.sub.2 C(Me).sub.2 CH.sub.2                      3.511        4-OCO.sub.2 Et                                                                              CH.sub.2 C(Me).sub.2 CH.sub.2                      3.512        4-NHCO.sub.2 Et                                                                             CH.sub.2 C(Me).sub.2 CH.sub.2                      3.513        4-CO.sub.2 Et CH.sub.2 C(Me).sub.2 CH.sub.2                      3.514        4-CONMe.sub.2 CH.sub.2 C(Me).sub.2 CH.sub.2                      3.515        H             CH.sub.2 CHCH                                      3.516        2-Me          CH.sub.2 CHCH                                      3.517        4-Me          CH.sub.2 CHCH                                      3.518        4-Et          CH.sub.2 CHCH                                      3.519        4-t-Bu        CH.sub.2 CHCH                                      3.520        2,4-Me.sub.2  CH.sub.2 CHCH                                      3.521        2,6-Me.sub.2  CH.sub.2 CHCH                                      3.522        3,4-Me.sub.2  CH.sub.2 CHCH                                      3.523        4-CF.sub.3    CH.sub.2 CHCH                                      3.524        2-Cl          CH.sub.2 CHCH                                      3.525        4-Cl          CH.sub.2 CHCH                                      3.526        2,4-Cl.sub.2  CH.sub.2 CHCH                                      3.527        2,6-Cl.sub.2  CH.sub.2 CHCH                                      3.528        2-F           CH.sub.2 CHCH                                      3.529        4-F           CH.sub.2 CHCH                                      3.530        2,4-F.sub.2   CH.sub.2 CHCH                                      3.531        2,6-F.sub.2   CH.sub.2 CHCH                                      3.532        4-Br          CH.sub.2 CHCH                                      3.533        4-NO.sub.2    CH.sub.2 CHCH                                      3.534        4-OMe         CH.sub.2 CHCH                                      3.535        4-SMe         CH.sub.2 CHCH                                      3.536        4-SO.sub.2 Me CH.sub.2 CHCH                                      3.537        4-OCHF.sub.2  CH.sub.2 CHCH                                      3.538        4-OCF.sub.3   CH.sub.2 CHCH                                      3.539        4-Ph          CH.sub.2 CHCH                                      3.540        4-OPh         CH.sub.2 CHCH                                      3.541        4-OCH.sub.2 Ph                                                                              CH.sub.2 CHCH                                      3.542        4-CHCHPh      CH.sub.2 CHCH                                      3.543        4-NH.sub.2    CH.sub.2 CHCH                                      3.544        4-OCO.sub.2 Et                                                                              CH.sub.2 CHCH                                      3.545        4-NHCO.sub.2 Et                                                                             CH.sub.2 CHCH                                      3.546        4-CO.sub.2 Et CH.sub.2 CHCH                                      3.547        4-CONMe.sub.2 CH.sub.2 CHCH                                      3.548        H             CH(Me)CHCH                                         3.549        2-Me          CH(Me)CHCH                                         3.550        4-Me          CH(Me)CHCH                                         3.551        4-Et          CH(Me)CHCH                                         3.552        4-t-Bu        CH(Me)CHCH                                         3.553        2,4-Me.sub.2  CH(Me)CHCH                                         3.554        2,6-Me.sub.2  CH(Me)CHCH                                         3.555        3,4-Me.sub.2  CH(Me)CHCH                                         3.556        4-CF.sub.3    CH(Me)CHCH                                         3.557        2-Cl          CH(Me)CHCH                                         3.558        4-Cl          CH(Me)CHCH                                         3.559        2,4-Cl.sub.2  CH(Me)CHCH                                         3.560        2,6-Cl.sub.2  CH(Me)CHCH                                         3.561        2-F           CH(Me)CHCH                                         3.562        4-F           CH(Me)CHCH                                         3.563        2,4-F.sub.2   CH(Me)CHCH                                         3.564        2,6-F.sub.2   CH(Me)CHCH                                         3.565        4-Br          CH(Me)CHCH                                         3.566        4-NO.sub.2    CH(Me)CHCH                                         3.567        4-OMe         CH(Me)CHCH                                         3.568        4-SMe         CH(Me)CHCH                                         3.569        4-SO.sub.2 Me CH(Me)CHCH                                         3.570        4-OCHF.sub.2  CH(Me)CHCH                                         3.571        4-OCF.sub.3   CH(Me)CHCH                                         3.572        4-Ph          CH(Me)CHCH                                         3.573        4-OPh         CH(Me)CHCH                                         3.574        4-OCH.sub.2 Ph                                                                              CH(Me)CHCH                                         3.575        4-CHCHPh      CH(Me)CHCH                                         3.576        4-NH.sub.2    CH(Me)CHCH                                         3.577        4-OCO.sub.2 Et                                                                              CH(Me)CHCH                                         3.578        4-NHCO.sub.2 Et                                                                             CH(Me)CHCH                                         3.579        4-CO.sub.2 Et CH(Me)CHCH                                         3.580        4-CONMe.sub.2 CH(Me)CHCH                                         3.581        H             CH.sub.2 C(Me)CH                                   3.582        2-Me          CH.sub.2 C(Me)CH                                   3.583        4-Me          CH.sub.2 C(Me)CH                                   3.584        4-Et          CH.sub.2 C(Me)CH                                   3.585        4-t-Bu        CH.sub.2 C(Me)CH                                   3.586        2,4-Me.sub.2  CH.sub.2 C(Me)CH                                   3.587        2,6-Me.sub.2  CH.sub.2 C(Me)CH                                   3.588        3,4-Me.sub.2  CH.sub.2 C(Me)CH                                   3.589        4-CF.sub.3    CH.sub.2 C(Me)CH                                   3.590        2-Cl          CH.sub.2 C(Me)CH                                   3.591        4-Cl          CH.sub.2 C(Me)CH                                   3.592        2,4-Cl.sub.2  CH.sub.2 C(Me)CH                                   3.593        2,6-Cl.sub.2  CH.sub.2 C(Me)CH                                   3.594        2-F           CH.sub.2 C(Me)CH                                   3.595        4-F           CH.sub.2 C(Me)CH                                   3.596        2,4-F.sub.2   CH.sub.2 C(Me)CH                                   3.597        2,6-F.sub.2   CH.sub.2 C(Me)CH                                   3.598        4-Br          CH.sub.2 C(Me)CH                                   3.599        4-NO.sub.2    CH.sub.2 C(Me)CH                                   3.600        4-OMe         CH.sub.2 C(Me)CH                                   3.601        4-SMe         CH.sub.2 C(Me)CH                                   3.602        4-SO.sub.2 Me CH.sub.2 C(Me)CH                                   3.603        4-OCHF.sub.2  CH.sub.2 C(Me)CH                                   3.604        4-OCF.sub.3   CH.sub.2 C(Me)CH                                   3.605        4-Ph          CH.sub.2 C(Me)CH                                   3.606        4-OPh         CH.sub.2 C(Me)CH                                   3.607        4-OCH.sub.2 Ph                                                                              CH.sub.2 C(Me)CH                                   3.608        4-CHCHPh      CH.sub.2 C(Me)CH                                   3.609        4-NH.sub.2    CH.sub.2 C(Me)CH                                   3.610        4-OCO.sub.2 Et                                                                              CH.sub.2 C(Me)CH                                   3.611        4-NHCO.sub.2 Et                                                                             CH.sub.2 C(Me)CH                                   3.612        4-CO.sub.2 Et CH.sub.2 C(Me)CH                                   3.613        4-CONMe.sub.2 CH.sub.2 C(Me)CH                                   3.614        H             CH.sub.2 CHC(Me)                                   3.615        2-Me          CH.sub.2 CHC(Me)                                   3.616        4-Me          CH.sub.2 CHC(Me)                                   3.617        4-Et          CH.sub.2 CHC(Me)                                   3.618        4-t-Bu        CH.sub.2 CHC(Me)                                   3.619        2,4-Me.sub.2  CH.sub.2 CHC(Me)                                   3.620        2,6-Me.sub.2  CH.sub.2 CHC(Me)                                   3.621        3,4-Me.sub.2  CH.sub.2 CHC(Me)                                   3.622        4-CF.sub.2    CH.sub.2 CHC(Me)                                   3.623        2-Cl          CH.sub.2 CHC(Me)                                   3.624        4-Cl          CH.sub.2 CHC(Me)                                   3.625        2,4-Cl.sub.2  CH.sub.2 CHC(Me)                                   3.626        2,6-Cl.sub.2  CH.sub.2 CHC(Me)                                   3.627        2-F           CH.sub.2 CHC(Me)                                   3.628        4-F           CH.sub.2 CHC(Me)                                   3.629        2,4-F.sub.2   CH.sub.2 CHC(Me)                                   3.630        2,6-F.sub.2   CH.sub.2 CHC(Me)                                   3.631        4-Br          CH.sub.2 CHC(Me)                                   3.632        4-NO.sub.2    CH.sub.2 CHC(Me)                                   3.633        4-OMe         CH.sub.2 CHC(Me)                                   3.634        4-SMe         CH.sub.2 CHC(Me)                                   3.635        4-SO.sub.2 Me CH.sub.2 CHC(Me)                                   3.636        4-OCHF.sub.2  CH.sub.2 CHC(Me)                                   3.637        4-OCF.sub.3   CH.sub.2 CHC(Me)                                   3.638        4-Ph          CH.sub.2 CHC(Me)                                   3.639        4-OPh         CH.sub.2 CHC(Me)                                   3.640        4-OCH.sub.2 Ph                                                                              CH.sub.2 CHC(Me)                                   3.641        4-CHCHPh      CH.sub.2 CHC(Me)                                   3.642        4-NH.sub.2    CH.sub.2 CHC(Me)                                   3.643        4-OCO.sub.2 Et                                                                              CH.sub.2 CHC(Me)                                   3.644        4-NHCO.sub.2 Et                                                                             CH.sub.2 CHC(Me)                                   3.645        4-CO.sub.2 Et CH.sub.2 CHC(Me)                                   3.646        4-CONMe.sub.2 CH.sub.2 CHC(Me)                                   3.647        H             (CH.sub.2).sub.2 O                                 3.648        2-Me          (CH.sub.2).sub.2 O                                 3.649        3-Me          (CH.sub.2).sub.2 O                                 3.650        4-Me          (CH.sub.2).sub.2 O                                 3.651        2-Et          (CH.sub.2).sub.2 O                                 3.652        3-Et          (CH.sub.2).sub.2 O                                 3.653        4-Et          (CH.sub.2).sub.2 O                                 3.654        2-Pr          (CH.sub.2).sub.2 O                                 3.655        3-Pr          (CH.sub.2).sub.2 O                                 3.656        4-Pr          (CH.sub.2).sub.2 O                                 3.657        2-i-Pr        (CH.sub.2).sub.2 O                                 3.658        3-i-Pr        (CH.sub.2).sub.2 O                                 3.659        4-i-Pr        (CH.sub.2).sub.2 O                                 3.660        2-t-Bu        (CH.sub.2).sub.2 O                                 3.661        3-t-Bu        (CH.sub.2).sub.2 O                                 3.662        4-t-Bu        (CH.sub.2).sub.2 O                                 3.663        2,4-Me.sub.2  (CH.sub.2).sub.2 O                                 3.664        2,5-Me.sub.2  (CH.sub.2).sub.2 O                                 3.665        2,6-Me.sub.2  (CH.sub.2).sub.2 O                                 3.666        3,4-Me.sub.2  (CH.sub.2).sub.2 O                                 3.667        2,4,6-Me.sub.3                                                                              (CH.sub.2).sub.2 O                                 3.668        4-t-Bu-2,6-Me.sub.2                                                                         (CH.sub.2).sub.2 O                                 3.669        3,5-(t-Bu).sub.2 -4-OH                                                                      (CH.sub.2).sub.2 O                                 3.670        2-CF.sub.3    (CH.sub.2).sub.2 O                                 3.671        3-CF.sub.3    (CH.sub.2).sub.2 O                                 3.672        4-CF.sub.3    (CH.sub.2).sub.2 O                                 3.673        2-Cl          (CH.sub.2).sub.2 O                                 3.674        3-Cl          (CH.sub.2).sub.2 O                                 3.675        4-Cl          (CH.sub.2).sub.2 O                                 3.676        2,4-Cl.sub.2  (CH.sub.2).sub.2 O                                 3.677        2,5-Cl.sub.2  (CH.sub.2).sub.2 O                                 3.678        2,6-Cl.sub.2  (CH.sub.2).sub.2 O                                 3.679        3,4-Cl.sub.2  (CH.sub.2).sub.2 O                                 3.680        2,4,6-Cl.sub.3                                                                              (CH.sub.2).sub.2 O                                 3.681        2-F           (CH.sub.2).sub.2 O                                 3.682        3-F           (CH.sub.2).sub.2 O                                 3.683        4-F           (CH.sub.2).sub.2 O                                 3.684        2,4-F.sub.2   (CH.sub.2).sub.2 O                                 3.685        3,4-F.sub.2   (CH.sub.2).sub.2 O                                 3.686        2,6-F.sub.2   (CH.sub.2).sub.2 O                                 3.687        2-Br          (CH.sub.2).sub.2 O                                 3.688        3-Br          (CH.sub.2).sub.2 O                                 3.689        4-Br          (CH.sub.2).sub.2 O                                 3.690        2,4-Br.sub.2  (CH.sub.2).sub.2 O                                 3.691        2,6-Br.sub.2  (CH.sub.2).sub.2 O                                 3.692        3,4-Br.sub.2  (CH.sub.2).sub.2 O                                 3.693        4-I           (CH.sub.2).sub.2 O                                 3.694        4-Cl-2-Me     (CH.sub.2).sub.2 O                                 3.695        2-NO.sub.2    (CH.sub.2).sub.2 O                                 3.696        3-NO.sub.2    (CH.sub.2).sub.2 O                                 3.697        4-NO.sub.2    (CH.sub.2).sub.2 O                                 3.698        2-Cl-4-NO.sub.2                                                                             (CH.sub.2).sub.2 O                                 3.699        3-Cl-4-NO.sub.2                                                                             (CH.sub.2).sub.2 O                                 3.700        4-Cl-3-NO.sub.2                                                                             (CH.sub.2).sub.2 O                                 3.701        4-OH          (CH.sub.2).sub.2 O                                 3.702        2-OMe         (CH.sub.2).sub.2 O                                 3.703        3-OMe         (CH.sub.2).sub.2 O                                 3.704        4-OMe         (CH.sub.2).sub.2 O                                 3.705        4-OBu         (CH.sub.2).sub.2 O                                 3.706        3,4-(OMe).sub.2                                                                             (CH.sub.2).sub.2 O                                 3.707        4-SMe         (CH.sub.2).sub.2 O                                 3.708        4-SOMe        (CH.sub.2).sub.2 O                                 3.709        4-SO.sub.2 Me (CH.sub.2).sub.2 O                                 3.710        4-OCHF.sub.2  (CH.sub.2).sub.2 O                                 3.711        4-OCF.sub.3   (CH.sub.2).sub.2 O                                 3.712        2-Ph          (CH.sub.2).sub.2 O                                 3.713        3-Ph          (CH.sub.2).sub.2 O                                 3.714        4-Ph          (CH.sub.2).sub.2 O                                 3.715        2-OPh         (CH.sub.2).sub.2 O                                 3.716        3-OPh         (CH.sub.2).sub.2 O                                 3.717        4-OPh         (CH.sub.2).sub.2 O                                 3.718        2-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2 O                                 3.719        3-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2 O                                 3.720        4-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.2 O                                 3.721        4-CHCHPh      (CH.sub.2).sub.2 O                                 3.722        4-NH.sub.2    (CH.sub.2).sub.2 O                                 3.723        4-NMe.sub.2   (CH.sub.2).sub.2 O                                 3.724        4-OCO.sub.2 Me                                                                              (CH.sub.2).sub.2 O                                 3.725        4-OCO.sub.2 Et                                                                              (CH.sub.2).sub.2 O                                 3.726        4-OCO.sub.2 t-Bu                                                                            (CH.sub.2).sub.2 O                                 3.727        3-Cl-4-OCO.sub.2 t-Bu                                                                       (CH.sub.2).sub.2 O                                 3.728        4-NHCO.sub.2 Me                                                                             (CH.sub.2).sub.2 O                                 3.729        4-NHCO.sub.2 Et                                                                             (CH.sub.2).sub.2 O                                 3.730        4-NHCO.sub.2 t-Bu                                                                           (CH.sub.2).sub.2 O                                 3.731        4-CO.sub.2 Me (CH.sub.2).sub.2 O                                 3.732        4-CO.sub.2 Et (CH.sub.2).sub.2 O                                 3.733        4-CONHMe      (CH.sub.2).sub.2 O                                 3.734        4-CONHEt      (CH.sub.2).sub.2 O                                 3.735        4-CONMe.sub.2 (CH.sub.2).sub.2 O                                 3.736        4-CONEt.sub.2 (CH.sub.2).sub.2 O                                 3.737        H             (CH.sub.2).sub.3 O                                 3.738        2-Me          (CH.sub.2).sub.3 O                                 3.739        3-Me          (CH.sub.2).sub.3 O                                 3.740        4-Me          (CH.sub.2).sub.3 O                                 3.741        4-Et          (CH.sub.2).sub.3 O                                 3.742        4-i-Pr        (CH.sub.2).sub.3 O                                 3.743        4-t-Bu        (CH.sub.2).sub.3 O                                 3.744        2,4-Me.sub.2  (CH.sub.2).sub.3 O                                 3.745        2,6-Me.sub.2  (CH.sub.2).sub.3 O                                 3.746        3,4-Me.sub.2  (CH.sub.2).sub.3 O                                 3.747        4-CF.sub.3    (CH.sub.2).sub.3 O                                 3.748        2-Cl          (CH.sub.2).sub.3 O                                 3.749        3-Cl          (CH.sub.2).sub.3 O                                 3.750        4-Cl          (CH.sub.2).sub.3 O                                 3.751        2,4-Cl.sub.2  (CH.sub.2).sub.3 O                                 3.752        2,6-Cl.sub.2  (CH.sub.2).sub.3 O                                 3.753        2-F           (CH.sub.2).sub.3 O                                 3.754        3-F           (CH.sub.2).sub.3 O                                 3.755        4-F           (CH.sub.2).sub.3 O                                 3.756        2,4-F.sub.2   (CH.sub.2).sub.3 O                                 3.757        2,6-F.sub.2   (CH.sub.2).sub.3 O                                 3.758        4-Br          (CH.sub.2).sub.3 O                                 3.759        2,4-Br.sub.2  (CH.sub.2).sub.3 O                                 3.760        4-I           (CH.sub.2).sub.3 O                                 3.761        4-NO.sub.2    (CH.sub.2).sub.3 O                                 3.762        4-OMe         (CH.sub.2).sub.3 O                                 3.763        3,4-(OMe).sub.2                                                                             (CH.sub.2).sub.3 O                                 3.764        4-SMe         (CH.sub.2).sub.3 O                                 3.765        4-SO.sub.2 Me (CH.sub.2).sub.3 O                                 3.766        4-OCHF.sub.2  (CH.sub.2).sub.3 O                                 3.767        4-OCF.sub.3   (CH.sub.2).sub.3 O                                 3.768        4-Ph          (CH.sub.2).sub.3 O                                 3.769        2-OPh         (CH.sub.2).sub.3 O                                 3.770        3-OPh         (CH.sub.2).sub.3 O                                 3.771        4-OPh         (CH.sub.2).sub.3 O                                 3.772        2-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3 O                                 3.773        3-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3 O                                 3.774        4-OCH.sub.2 Ph                                                                              (CH.sub.2).sub.3 O                                 3.775        4-CHCHPh      (CH.sub.2).sub.3 O                                 3.776        4-NH.sub.2    (CH.sub.2).sub.3 O                                 3.777        4-OCO.sub.2 Et                                                                              (CH.sub.2).sub.3 O                                 3.778        4-NHCO.sub.2 Et                                                                             (CH.sub.2).sub.3 O                                 3.779        4-CO.sub.2 Et (CH.sub.2).sub.3 O                                 3.780        4-CONMe.sub.2 (CH.sub.2).sub.3 O                                 ______________________________________                                    

                                      TABLE 4                                     __________________________________________________________________________    In the compounds of                                                            ##STR13##                                                                     ##STR14##                                                                     ##STR15##                                                                     ##STR16##                                                                     ##STR17##                                                                     ##STR18##                                                                    or                                                                             ##STR19##                                                                    Compound No.                                                                          E         G    J                                                      __________________________________________________________________________    4.1     H                                                                     4.2     Me                                                                    4.3     Et                                                                    4.4     Pr                                                                    4.5     i-Pr                                                                  4.6     Bu                                                                    4.7     s-Bu                                                                  4.8     i-Bu                                                                  4.9     t-Bu                                                                  4.10    Pen                                                                   4.11    CH(Me)CH.sub.2 CH.sub.2 CH.sub.3                                      4.12    CH.sub.2 CH(Me)CH.sub.2 CH.sub.3                                      4.13    (CH.sub.2).sub.2 CH(Me).sub.2                                         4.14    CH.sub.2 C(Me).sub.3                                                  4.15    Hex                                                                   4.16    CH(Me)C(Me).sub.3                                                     4.17    cyc-Pr                                                                4.18    CH.sub.2 cyc-Pr                                                       4.19    CH.sub.2 (1-CH.sub.3 -cyc-Pr)                                         4.20    cyc-Bu                                                                4.21    cyc-Pen                                                               4.22    cyc-Hex                                                               4.23    CH.sub.2 cyc-Hex                                                      4.24    (CH.sub.2).sub.2 cyc-Hex                                              4.25    (4-t-Bu)-cyc-Hex                                                      4.26    (4-Ph)-cyc-Hex                                                        4.27    CH.sub.2 CHCH.sub.2                                                   4.28    (CH.sub.2).sub.2 CHCH.sub.2                                           4.29    CH(Me)CHCH.sub.2                                                      4.30    CH.sub.2 C(Me)CH.sub.2                                                4.31    CH.sub.2 CHCHMe                                                       4.32    C(Me).sub.2 CHCH.sub.2                                                4.33    CH.sub.2 C(Me)CHMe                                                    4.34    CH.sub.2 CHC(Me).sub.2                                                4.35    (CH.sub.2).sub.3 CHCH.sub.2                                           4.36    CH.sub.2 C(Me)C(Me).sub.2                                             4.37    CH.sub.2 C CH                                                         4.38    CH(Me)C CH                                                            4.39    C(Me).sub.2 C CH                                                      4.40    CH.sub.2 C CMe                                                        4.41    (CH.sub.2).sub.2 C CEt                                                4.42    (CH.sub.2).sub.2 Cl                                                   4.43    (CH.sub.2).sub.2 Br                                                   4.44    (CH.sub.2).sub.2 I                                                    4.45    (CH.sub.2).sub.2 F                                                    4.46    CH.sub.2 CHCl.sub.2                                                   4.47    CH.sub.2 CHBr.sub.2                                                   4.48    CH.sub.2 CHF.sub.2                                                    4.49    CH.sub.2 CCl.sub.3                                                    4.50    CH.sub.2 CBr.sub.3                                                    4.51    CH.sub.2 CF.sub.3                                                     4.52    (CH.sub.2).sub.3 Cl                                                   4.53    (CH.sub.2).sub.3 Br                                                   4.54    (CH.sub.2).sub.3 F                                                    4.55    CH.sub.2 CHClCH.sub.2 Cl                                              4.56    CH.sub.2 CHBrCH.sub.2 Br                                              4.57    CH.sub.2 CHFCH.sub.2 F                                                4.58    CH(CH.sub.2 Cl).sub.2                                                 4.59    CH(CH.sub.2 Br).sub.2                                                 4.60    CH(CH.sub.2 F).sub.2                                                  4.61    CH.sub.2 C(Cl)CH.sub.2                                                4.62    CH.sub.2 CHCHCl                                                       4.63    CH.sub.2 CHCCl.sub.2                                                  4.64    CH.sub.2 C(Cl)CHCl                                                    4.65    CH.sub.2 COMe                                                         4.66    CH.sub.2 COPh                                                         4.67    (CH.sub.2).sub.2 COMe                                                 4.68    (CH.sub.2).sub.2 COPh                                                 4.69    CH(CO.sub.2 Me).sub.2                                                 4.70    CH(CO.sub.2 Et).sub.2                                                 4.71    CH(CN)CO.sub.2 Me                                                     4.72    CH(COMe)CO.sub.2 Me                                                   4.73    CH(Ph).sub.2                                                          4.74    CH.sub.2 CH(PH).sub.2                                                 4.75    W.sub.1                                                               4.76    W.sub.2                                                               4.77    W.sub.3                                                               4.78    W.sub.4                                                               4.79    W.sub.5                                                               4.80    W.sub.6                                                               4.81    W.sub.7                                                               4.82    W.sub.8                                                               4.83    W.sub.9                                                               4.84    W.sub.10                                                              4.85    W.sub.11                                                              4.86    W.sub.12                                                              4.87    W.sub.13                                                              4.88    W.sub.14                                                              4.89    W.sub.15                                                              4.90    W.sub.16                                                              4.91    W.sub.17                                                              4.92    W.sub.18                                                              4.93    W.sub.19                                                              4.94    W.sub.20                                                              4.95    CH.sub.2  CN                                                          4.96    (CH.sub.2).sub.2                                                                        CN                                                          4.97    CH(Me)    CN                                                          4.98    (CH.sub.2).sub.3                                                                        CN                                                          4.99    CH.sub.2 CH(Me)                                                                         CN                                                          4.100   CH(Me)CH.sub.2                                                                          CN                                                          4.101   (CH.sub.2).sub.4                                                                        CN                                                          4.102   CH(Me)CH(Me)                                                                            CN                                                          4.103   CH.sub.2 C(Me).sub.2                                                                    CN                                                          4.104   CH.sub.2 C(Me).sub.2 CH.sub.2                                                           CN                                                          4.105   CH.sub.2  O    Me                                                     4.106   CH.sub.2  O    Et                                                     4.107   CH.sub.2  O    Pr                                                     4.108   CH.sub.2  O    i-Pr                                                   4.109   CH.sub.2  O    Bu                                                     4.110   CH.sub.2  O    s-Bu                                                   4.111   CH.sub.2  O    i-Bu                                                   4.112   CH.sub.2  O    t-Bu                                                   4.113   CH.sub.2  O    Pen                                                    4.114   CH.sub.2  O    Hex                                                    4.115   CH.sub.2  O    cyc-Pr                                                 4.116   CH.sub.2  O    cyc-Bu                                                 4.117   CH.sub.2  O    cyc-Pen                                                4.118   CH.sub.2  O    cyc-Hex                                                4.119   CH.sub.2  O    CH.sub.2 CCl.sub.3                                     4.120   CH.sub.2  O    CH.sub.2 CBr.sub.3                                     4.121   CH.sub.2  O    CH.sub.2 CF.sub.3                                      4.122   CH.sub.2  O    CH.sub.2 Ph                                            4.123   CH.sub.2  O    (CH.sub.2).sub.2 OMe                                   4.124   CH.sub.2  O    (CH.sub.2).sub.2 OEt                                   4.125   (CH.sub.2).sub.2                                                                        O    H                                                      4.126   (CH.sub.2).sub.2                                                                        O    Me                                                     4.127   (CH.sub.2).sub.2                                                                        O    Et                                                     4.128   (CH.sub.2).sub.2                                                                        O    Pr                                                     4.129   (CH.sub.2).sub.2                                                                        O    i-Pr                                                   4.130   (CH.sub.2).sub.2                                                                        O    Bu                                                     4.131   (CH.sub.2).sub.2                                                                        O    s-Bu                                                   4.132   (CH.sub.2).sub.2                                                                        O    i-Bu                                                   4.133   (CH.sub.2).sub.2                                                                        O    t-Bu                                                   4.134   (CH.sub.2).sub.2                                                                        O    Pen                                                    4.135   (CH.sub.2).sub.2                                                                        O    CH(Me)CH.sub.2 CH.sub.2 CH.sub.3                       4.136   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CH(Me)CH.sub.2 CH.sub.3                       4.137   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 CH(Me).sub.2                          4.138   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Me).sub.3                                   4.139   (CH.sub.2).sub.2                                                                        O    Hex                                                    4.140   (CH.sub.2).sub.2                                                                        O    cyc-Pr                                                 4.141   (CH.sub.2).sub.2                                                                        O    cyc-Bu                                                 4.142   (CH.sub.2).sub.2                                                                        O    cyc-Pen                                                4.143   (CH.sub.2).sub.2                                                                        O    cyc-Hex                                                4.144   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHCH.sub.2                                    4.145   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 CHCH.sub.2                            4.146   (CH.sub.2).sub.2                                                                        O    CH(Me)CHCH.sub.2                                       4.147   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Me)CH.sub.2                                 4.148   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHCHMe                                        4.149   (CH.sub.2).sub.2                                                                        O    C(Me).sub.2 CHCH.sub.2                                 4.150   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Me)CHMe                                     4.151   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHC(Me).sub.2                                 4.152   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.3 CHCH.sub.2                            4.153   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Me)C(Me).sub.2                              4.154   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C CH                                          4.155   (CH.sub.2).sub.2                                                                        O    CH(Me)C CH                                             4.156   (CH.sub.2).sub.2                                                                        O    C(Me).sub.2 C CH                                       4.157   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C CMe                                         4.158   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C CEt                                         4.159   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 Cl                                    4.160   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 Br                                    4.161   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 I                                     4.162   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 F                                     4.163   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHCl.sub.2                                    4.164   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHBr.sub.2                                    4.165   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHF.sub.2                                     4.166   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CCl.sub.3                                     4.167   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CBr.sub.3                                     4.168   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CF.sub.3                                      4.169   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.3 Cl                                    4.170   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.3 Br                                    4.171   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.3 F                                     4.172   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHClCH.sub.2 Cl                               4.173   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHBrCH.sub.2 Br                               4.174   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHFCH.sub.2 F                                 4.175   (CH.sub.2).sub.2                                                                        O    CH(CH.sub.2 Cl).sub.2                                  4.176   (CH.sub.2).sub.2                                                                        O    CH(CH.sub.2 Br).sub.2                                  4.177   (CH.sub.2).sub.2                                                                        O    CH(CH.sub.2 F).sub.2                                   4.178   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Cl)CH.sub.2                                 4.179   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHCHCl                                        4.180   (CH.sub.2).sub.2                                                                        O    CH.sub.2 CHCCl.sub.2                                   4.181   (CH.sub.2).sub.2                                                                        O    CH.sub.2 C(Cl)CHCl                                     4.182   (CH.sub.2).sub.2                                                                        O    CH.sub.2 Ph                                            4.183   (CH.sub.2).sub.2                                                                        O    CH.sub.2 COMe                                          4.184   (CH.sub.2).sub.2                                                                        O    CH.sub.2 COPh                                          4.185   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 COMe                                  4.186   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 NMe.sub.2                             4.187   (CH.sub.2).sub.2                                                                        O    CONHMe                                                 4.188   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OMe                                   4.189   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OEt                                   4.190   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OPr                                   4.191   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OBu                                   4.192   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 Ot-Bu                                 4.193   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OCH.sub.2 CHCH.sub.2                  4.194   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OCH.sub.2 C CH                        4.195   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 O(CH.sub.2).sub.2 Cl                  4.196   (CH.sub.2).sub.2                                                                        O    (CH.sub.2).sub.2 OPh                                   4.197   (CH.sub.2).sub.2                                                                        O    W.sub.21                                               4.198   CH(Me)    O    Me                                                     4.199   CH(Me)    O    Et                                                     4.200   CH(Me)    O    Pr                                                     4.201   CH(Me)    O    Bu                                                     4.202   (CH.sub.2).sub.3                                                                        O    H                                                      4.203   (CH.sub.2).sub.3                                                                        O    Me                                                     4.204   (CH.sub.2).sub.3                                                                        O    Et                                                     4.205   (CH.sub.2).sub.3                                                                        O    Pr                                                     4.206   (CH.sub.2).sub.3                                                                        O    i-Pr                                                   4.207   (CH.sub.2).sub.3                                                                        O    Bu                                                     4.208   (CH.sub.2).sub.3                                                                        O    s-Bu                                                   4.209   (CH.sub.2).sub.3                                                                        O    i-Bu                                                   4.210   (CH.sub.2).sub.3                                                                        O    t-Bu                                                   4.211   (CH.sub.2).sub.3                                                                        O    Pen                                                    4.212   (CH.sub.2).sub.3                                                                        O    CH(Me)CH.sub.2 CH.sub.2 CH.sub.3                       4.213   (CH.sub.2).sub.3                                                                        O    CH.sub.2 CH(Me)CH.sub.2 CH.sub.3                       4.214   (CH.sub.2).sub.3                                                                        O    (CH.sub.2).sub.2 CH(Me).sub.2                          4.215   (CH.sub.2).sub.3                                                                        O    CH.sub.2 C(Me).sub.3                                   4.216   (CH.sub.2).sub.3                                                                        O    Hex                                                    4.217   (CH.sub.2).sub.3                                                                        O    cyc-Pr                                                 4.218   (CH.sub.2).sub.3                                                                        O    cyc-Bu                                                 4.219   (CH.sub.2).sub.3                                                                        O    cyc-Pen                                                4.220   (CH.sub.2).sub.3                                                                        O    cyc-Hex                                                4.221   (CH.sub.2).sub.3                                                                        O    CH.sub.2 CHCH.sub.2                                    4.222   (CH.sub.2).sub.3                                                                        O    (CH.sub.2).sub.2 CHCH.sub.2                            4.223   (CH.sub.2).sub.3                                                                        O    CH(Me)CHCH.sub.2                                       4.224   (CH.sub.2).sub.3                                                                        O    CH.sub.2 C(Me)CH.sub.2                                 4.225   (CH.sub.2).sub.3                                                                        O    CH.sub.2 CHCHMe                                        4.226   (CH.sub.2).sub.3                                                                        O    CH.sub.2 C CH                                          4.227   (CH.sub.2).sub.3                                                                        O    CH(Me)C CH                                             4.228   (CH.sub.2).sub.3                                                                        O    CH.sub.2 C CMe                                         4.229   (CH.sub.2).sub.3                                                                        O    (CH.sub.2).sub.2 Cl                                    4.230   (CH.sub.2).sub.3                                                                        O    CH.sub.2 CHCl.sub.2                                    4.231   (CH.sub.2).sub.3                                                                        O    CH.sub.2 CCl.sub.3                                     4.232   CH.sub.2 CH(Me)                                                                         O    H                                                      4.233   CH.sub.2 CH(Me)                                                                         O    Me                                                     4.234   CH.sub.2 CH(Me)                                                                         O    Et                                                     4.235   CH.sub.2 CH(Me)                                                                         O    Pr                                                     4.236   CH.sub.2 CH(Me)                                                                         O    i-Pr                                                   4.237   CH.sub.2 CH(Me)                                                                         O    Bu                                                     4.238   CH.sub.2 CH(Me)                                                                         O    s-Bu                                                   4.239   CH.sub.2 CH(Me)                                                                         O    i-Bu                                                   4.240   CH.sub.2 CH(Me)                                                                         O    t-Bu                                                   4.241   CH.sub.2 CH(Me)                                                                         O    Pen                                                    4.242   CH.sub.2 CH(Me)                                                                         O    Hex                                                    4.243   CH.sub.2 CH(Me)                                                                         O    CH.sub.2 CHCH.sub.2                                    4.244   CH.sub.2 CH(Me)                                                                         O    CH.sub.2 C CH                                          4.245   CH.sub.2 CH(Me)                                                                         O    (CH.sub.2).sub.2 Cl                                    4.246   CH.sub.2 CH(Me)                                                                         O    CH.sub.2 CHCl.sub.2                                    4.247   CH.sub.2 CH(Me)                                                                         O    CH.sub.2 CCl.sub.3                                     4.248   CH(Me)CH.sub.2                                                                          O    H                                                      4.249   CH(Me)CH.sub.2                                                                          O    Me                                                     4.250   CH(Me)CH.sub.2                                                                          O    Et                                                     4.251   CH(Me)CH.sub.2                                                                          O    Pr                                                     4.252   CH(Me)CH.sub.2                                                                          O    i-Pr                                                   4.253   CH(Me)CH.sub.2                                                                          O    Bu                                                     4.254   CH(Me)CH.sub.2                                                                          O    s-Bu                                                   4.255   CH(Me)CH.sub.2                                                                          O    i-Bu                                                   4.256   CH(Me)CH.sub.2                                                                          O    t-Bu                                                   4.257   CH(Me)CH.sub.2                                                                          O    Pen                                                    4.258   CH(Me)CH.sub.2                                                                          O    Hex                                                    4.259   CH(Me)CH.sub.2                                                                          O    CH.sub.2 CHCH.sub.2                                    4.260   CH(Me)CH.sub.2                                                                          O    CH.sub.2 C CH                                          4.261   CH(Me)CH.sub.2                                                                          O    (CH.sub.2).sub.2 Cl                                    4.262   CH(Me)CH.sub.2                                                                          O    CH.sub.2 CHCl.sub.2                                    4.263   CH(Me)CH.sub.2                                                                          O    CH.sub.2 CCl.sub.3                                     4.264   (CH.sub.2).sub.4                                                                        O    H                                                      4.265   (CH.sub.2).sub.4                                                                        O    Me                                                     4.266   (CH.sub.2).sub.4                                                                        O    Et                                                     4.267   (CH.sub.2).sub.4                                                                        O    Pr                                                     4.268   (CH.sub.2).sub.4                                                                        O    i-Pr                                                   4.269   (CH.sub.2).sub.4                                                                        O    Bu                                                     4.270   (CH.sub.2).sub.4                                                                        O    s-Bu                                                   4.271   (CH.sub.2).sub.4                                                                        O    i-Bu                                                   4.272   (CH.sub.2).sub.4                                                                        O    t-Bu                                                   4.273   (CH.sub.2).sub.4                                                                        O    Pen                                                    4.274   (CH.sub.2).sub.4                                                                        O    Hex                                                    4.275   (CH.sub.2).sub.4                                                                        O    CH.sub.2 CHCH.sub.2                                    4.276   (CH.sub.2).sub.4                                                                        O    CH.sub.2 C CH                                          4.277   (CH.sub.2).sub.4                                                                        O    (CH.sub.2).sub.2 Cl                                    4.278   (CH.sub.2).sub.4                                                                        O    CH.sub.2 CHCl.sub.2                                    4.279   (CH.sub.2).sub.4                                                                        O    CH.sub.2 CCl.sub.3                                     4.280   CH(Me)CH(Me)                                                                            O    H                                                      4.281   CH(Me)CH(Me)                                                                            O    Me                                                     4.282   CH(Me)CH(Me)                                                                            O    Et                                                     4.283   CH(Me)CH(Me)                                                                            O    Pr                                                     4.284   CH(Me)CH(Me)                                                                            O    i-Pr                                                   4.285   CH(Me)CH(Me)                                                                            O    Bu                                                     4.286   CH(Me)CH(Me)                                                                            O    s-Bu                                                   4.287   CH(Me)CH(Me)                                                                            O    i-Bu                                                   4.288   CH(Me)CH(Me)                                                                            O    t-Bu                                                   4.289   CH(Me)CH(Me)                                                                            O    Pen                                                    4.290   CH(Me)CH(Me)                                                                            O    Hex                                                    4.291   CH(Me)CH(Me)                                                                            O    CH.sub.2 CHCH.sub.2                                    4.292   CH(Me)CH(Me)                                                                            O    CH.sub.2 C CH                                          4.293   CH(Me)CH(Me)                                                                            O    (CH.sub.2).sub.2 Cl                                    4.294   CH(Me)CH(Me)                                                                            O    CH.sub.2 CHCl.sub.2                                    4.295   CH(Me)CH(Me)                                                                            O    CH.sub.2 CCl.sub.3                                     4.296   CH.sub.2  CO.sub.2                                                                           H                                                      4.297   CH.sub.2  CO.sub.2                                                                           Me                                                     4.298   CH.sub.2  CO.sub.2                                                                           Et                                                     4.299   CH.sub.2  CO.sub.2                                                                           Pr                                                     4.300   CH.sub.2  CO.sub.2                                                                           i-Pr                                                   4.301   CH.sub.2  CO.sub.2                                                                           Bu                                                     4.302   CH.sub.2  CO.sub.2                                                                           s-Bu                                                   4.303   CH.sub.2  CO.sub.2                                                                           i-Bu                                                   4.304   CH.sub.2  CO.sub.2                                                                           t-Bu                                                   4.305   CH.sub.2  CO.sub.2                                                                           Pen                                                    4.306   CH.sub.2  CO.sub.2                                                                           CH(Me)CH.sub.2 CH.sub.2 CH.sub.3                       4.307   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CH(Me)CH.sub.2 CH.sub.3                       4.308   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 CH(Me).sub.2                          4.309   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Me).sub.3                                   4.310   CH.sub.2  CO.sub.2                                                                           Hex                                                    4.311   CH.sub.2  CO.sub.2                                                                           CH(Me)C(Me).sub.3                                      4.312   CH.sub.2  CO.sub.2                                                                           cyc-Pr                                                 4.313   CH.sub.2  CO.sub.2                                                                           CH.sub.2 cyc-Pr                                        4.314   CH.sub.2  CO.sub.2                                                                           CH.sub.2 (1-CH.sub.3 -cyc-Pr)                          4.315   CH.sub.2  CO.sub.2                                                                           cyc-Bu                                                 4.316   CH.sub.2  CO.sub.2                                                                           cyc-Pen                                                4.317   CH.sub.2  CO.sub.2                                                                           cyc-Hex                                                4.318   CH.sub.2  CO.sub.2                                                                           CH.sub.2 cyc-Hex                                       4.319   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 cyc-Hex                               4.320   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.321   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 CHCH.sub.2                            4.322   CH.sub.2  CO.sub.2                                                                           CH(Me)CHCH.sub.2                                       4.323   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Me)CH.sub.2                                 4.324   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHCHMe                                        4.325   CH.sub.2  CO.sub.2                                                                           C(Me).sub.2 CHCH.sub.2                                 4.326   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Me)CHMe                                     4.327   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHC(Me).sub.2                                 4.328   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.3 CHCH.sub.2                            4.329   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Me)C(Me).sub.2                              4.330   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C CH                                          4.331   CH.sub.2  CO.sub.2                                                                           CH(Me)C CH                                             4.332   CH.sub.2  CO.sub.2                                                                           C(Me).sub.2 C CH                                       4.333   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C CMe                                         4.334   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C CEt                                         4.335   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 Cl                                    4.336   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 Br                                    4.337   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 I                                     4.338   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 F                                     4.339   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHCl.sub.2                                    4.340   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHBr.sub.2                                    4.341   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHF.sub.2                                     4.342   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CCl.sub.3                                     4.343   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CBr.sub.3                                     4.344   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CF.sub.3                                      4.345   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.3 Cl                                    4.346   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.3 Br                                    4.347   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.3 F                                     4.348   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHClCH.sub.2 Cl                               4.349   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHBrCH.sub.2 Br                               4.350   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHFCH.sub.2 F                                 4.351   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Cl)CH.sub.2                                 4.352   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHCHCl                                        4.353   CH.sub.2  CO.sub.2                                                                           CH.sub.2 CHCCl.sub.2                                   4.354   CH.sub.2  CO.sub.2                                                                           CH.sub.2 C(Cl)CHCl                                     4.355   CH.sub.2  CO.sub.2                                                                           CH.sub.2 COMe                                          4.356   CH.sub.2  CO.sub.2                                                                           CH.sub.2 COPh                                          4.357   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 COMe                                  4.358   CH.sub.2  CO.sub.2                                                                           (CH.sub.2).sub.2 COPh                                  4.359   CH.sub.2  CO.sub.2                                                                           W.sub.1                                                4.360   CH.sub.2  CO.sub.2                                                                           W.sub.2                                                4.361   CH.sub.2  CO.sub.2                                                                           W.sub.3                                                4.362   CH.sub.2  CO.sub.2                                                                           W.sub.4                                                4.363   CH(Me)    CO.sub.2                                                                           H                                                      4.364   CH(Me)    CO.sub.2                                                                           Me                                                     4.365   CH(Me)    CO.sub.2                                                                           Et                                                     4.366   CH(Me)    CO.sub.2                                                                           Pr                                                     4.367   CH(Me)    CO.sub.2                                                                           i-Pr                                                   4.368   CH(Me)    CO.sub.2                                                                           Bu                                                     4.369   CH(Me)    CO.sub.2                                                                           s-Bu                                                   4.370   CH(Me)    CO.sub.2                                                                           i-Bu                                                   4.371   CH(Me)    CO.sub.2                                                                           t-Bu                                                   4.372   CH(Me)    CO.sub.2                                                                           Pen                                                    4.373   CH(Me)    CO.sub.2                                                                           CH(Me)CH.sub.2 CH.sub.2 CH.sub.3                       4.374   CH(Me)    CO.sub.2                                                                           CH.sub.2 CH(Me)CH.sub.2 CH.sub.3                       4.375   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 CH(Me).sub.2                          4.376   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Me).sub.3                                   4.377   CH(Me)    CO.sub.2                                                                           Hex                                                    4.378   CH(Me)    CO.sub.2                                                                           CH(Me)C(Me).sub.3                                      4.379   CH(Me)    CO.sub.2                                                                           cyc-Pr                                                 4.380   CH(Me)    CO.sub.2                                                                           CH.sub.2 cyc-Pr                                        4.381   CH(Me)    CO.sub.2                                                                           CH.sub.2 (1-CH.sub.3 -cyc-Pr)                          4.382   CH(Me)    CO.sub.2                                                                           cyc-Bu                                                 4.383   CH(Me)    CO.sub.2                                                                           cyc-Pen                                                4.384   CH(Me)    CO.sub.2                                                                           cyc-Hex                                                4.385   CH(Me)    CO.sub.2                                                                           CH.sub.2 cyc-Hex                                       4.386   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 cyc-Hex                               4.387   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.388   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 CHCH.sub.2                            4.389   CH(Me)    CO.sub.2                                                                           CH(Me)CHCH.sub.2                                       4.390   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Me)CH.sub.2                                 4.391   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHCHMe                                        4.392   CH(Me)    CO.sub.2                                                                           C(Me).sub.2 CHCH.sub.2                                 4.393   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Me)CHMe                                     4.394   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHC(Me).sub.2                                 4.395   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.3 CHCH.sub.2                            4.396   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Me)C(Me).sub.2                              4.397   CH(Me)    CO.sub.2                                                                           CH.sub.2 C CH                                          4.398   CH(Me)    CO.sub.2                                                                           CH(Me)C CH                                             4.399   CH(Me)    CO.sub.2                                                                           C(Me).sub.2 C CH                                       4.400   CH(Me)    CO.sub.2                                                                           CH.sub.2 C CMe                                         4.401   CH(Me)    CO.sub.2                                                                           CH.sub.2 C CEt                                         4.402   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 Cl                                    4.403   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 Br                                    4.404   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 I                                     4.405   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.2 F                                     4.406   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHCl.sub.2                                    4.407   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHBr.sub.2                                    4.408   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHF.sub.2                                     4.409   CH(Me)    CO.sub.2                                                                           CH.sub.2 CCl.sub.3                                     4.410   CH(Me)    CO.sub.2                                                                           CH.sub.2 CBr.sub.3                                     4.411   CH(Me)    CO.sub.2                                                                           CH.sub.2 CF.sub.3                                      4.412   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.3 Cl                                    4.413   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.3 Br                                    4.414   CH(Me)    CO.sub.2                                                                           (CH.sub.2).sub.3 F                                     4.415   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHClCH.sub.2 Cl                               4.416   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHBrCH.sub.2 Br                               4.417   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHFCH.sub.2 F                                 4.418   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Cl)CH.sub.2                                 4.419   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHCHCl                                        4.420   CH(Me)    CO.sub.2                                                                           CH.sub.2 CHCCl.sub.2                                   4.421   CH(Me)    CO.sub.2                                                                           CH.sub.2 C(Cl)CHCl                                     4.422   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           H                                                      4.423   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Me                                                     4.424   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Et                                                     4.425   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Pr                                                     4.426   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           i-Pr                                                   4.427   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Bu                                                     4.428   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Pen                                                    4.429   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           Hex                                                    4.430   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           cyc-Pr                                                 4.431   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           cyc-Bu                                                 4.432   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           cyc-Pen                                                4.433   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           cyc-Hex                                                4.434   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.435   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           CH.sub.2 C CH                                          4.436   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           (CH.sub.2).sub.2 Cl                                    4.437   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           CH.sub.2 CHCl.sub.2                                    4.438   (CH.sub.2).sub.2                                                                        CO.sub.2                                                                           CH.sub.2 CCl.sub.3                                     4.439   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           H                                                      4.440   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Me                                                     4.441   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Et                                                     4.442   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Pr                                                     4.443   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           i-Pr                                                   4.444   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Bu                                                     4.445   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Pen                                                    4.446   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           Hex                                                    4.447   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           cyc-Pr                                                 4.448   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           cyc-Bu                                                 4.449   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           cyc-Pen                                                4.450   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           cyc-Hex                                                4.451   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.452   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           CH.sub.2 C CH                                          4.453   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           (CH.sub.2).sub.2 Cl                                    4.454   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           CH.sub.2 CHCl.sub.2                                    4.455   (CH.sub.2).sub.3                                                                        CO.sub.2                                                                           CH.sub.2 CCl.sub.3                                     4.456   CH.sub.2  S    H                                                      4.457   CH.sub.2  S    Me                                                     4.458   CH.sub.2  S    Et                                                     4.459   CH.sub.2  S    Pr                                                     4.460   (CH.sub.2).sub.2                                                                        S    Me                                                     4.461   (CH.sub.2).sub.2                                                                        S    Et                                                     4.462   (CH.sub.2).sub.2                                                                        S    Pr                                                     4.463   (CH.sub.2).sub.2                                                                        S    Bu                                                     4.464   (CH.sub.2).sub.2                                                                        S    CH.sub.2 CHCH.sub.2                                    4.465   (CH.sub.2).sub.3                                                                        S    Me                                                     4.466   (CH.sub.2).sub.3                                                                        S    Et                                                     4.467   (CH.sub.2).sub.3                                                                        S    Pr                                                     4.468   (CH.sub.2).sub.3                                                                        S    Bu                                                     4.469   (CH.sub.2).sub.3                                                                        S    CH.sub.2 CHCH.sub.2                                    4.470   CH.sub.2  SO   Me                                                     4.471   CH.sub.2  SO   Et                                                     4.472   CH.sub.2  SO   Pr                                                     4.473   CH.sub.2  SO   Bu                                                     4.474   CH.sub.2  SO   CH.sub.2 CHCH.sub.2                                    4.475   (CH.sub.2).sub.2                                                                        SO   Me                                                     4.476   (CH.sub.2).sub.2                                                                        SO   Et                                                     4.477   (CH.sub.2).sub.2                                                                        SO   Pr                                                     4.478   (CH.sub.2).sub.2                                                                        SO   Bu                                                     4.479   (CH.sub.2).sub.2                                                                        SO   CH.sub.2 CHCH.sub.2                                    4.480   (CH.sub.2).sub.3                                                                        SO   Me                                                     4.481   (CH.sub.2).sub.3                                                                        SO   Et                                                     4.482   (CH.sub.2).sub.3                                                                        SO   Pr                                                     4.483   (CH.sub.2).sub.3                                                                        SO   Bu                                                     4.484   (CH.sub.2).sub.3                                                                        SO   CH.sub.2 CHCH.sub.2                                    4.485   CH.sub.2  SO.sub.2                                                                           Me                                                     4.486   CH.sub.2  SO.sub.2                                                                           Et                                                     4.487   CH.sub.2  SO.sub.2                                                                           Pr                                                     4.488   CH.sub.2  SO.sub.2                                                                           Bu                                                     4.489   CH.sub.2  SO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.490   (CH.sub.2).sub.2                                                                        SO.sub.2                                                                           Me                                                     4.491   (CH.sub.2).sub.2                                                                        SO.sub.2                                                                           Et                                                     4.492   (CH.sub.2).sub.2                                                                        SO.sub.2                                                                           Pr                                                     4.493   (CH.sub.2).sub.2                                                                        SO.sub.2                                                                           Bu                                                     4.494   (CH.sub.2).sub.2                                                                        SO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    4.495   (CH.sub.2).sub.3                                                                        SO.sub.2                                                                           Me                                                     4.496   (CH.sub.2).sub.3                                                                        SO.sub.2                                                                           Et                                                     4.497   (CH.sub.2).sub.3                                                                        SO.sub.2                                                                           Pr                                                     4.498   (CH.sub.2).sub.3                                                                        SO.sub.2                                                                           Bu                                                     4.499   (CH.sub.2).sub.3                                                                        SO.sub.2                                                                           CH.sub.2 CHCH.sub.2                                    W.sub.1 -W.sub.21 in the table 4 show the following structures.               W.sub.1 :                                                                                   ##STR20##                                                       W.sub.2 :                                                                                   ##STR21##                                                       W.sub.3 :                                                                                   ##STR22##                                                       W.sub.4 :                                                                                   ##STR23##                                                       W.sub.5 :                                                                                   ##STR24##                                                       W.sub.6 :                                                                                   ##STR25##                                                       W.sub.7 :                                                                                   ##STR26##                                                       W.sub.8 :                                                                                   ##STR27##                                                       W.sub.9 :                                                                                   ##STR28##                                                       W.sub.10 :                                                                                  ##STR29##                                                       W.sub.11 :                                                                                  ##STR30##                                                       W.sub.12 :                                                                                  ##STR31##                                                       W.sub.13 :                                                                                  ##STR32##                                                       W.sub.14 :                                                                                  ##STR33##                                                       W.sub.15 :                                                                                  ##STR34##                                                       W.sub.16 :                                                                                  ##STR35##                                                       W.sub.17 :                                                                                  ##STR36##                                                       W.sub.18 :                                                                                  ##STR37##                                                       W.sub.19 :                                                                                  ##STR38##                                                       W.sub.20 :                                                                                  ##STR39##                                                       W.sub.21 :                                                                                  ##STR40##                                                       __________________________________________________________________________

                  TABLE 5                                                         ______________________________________                                        In the compounds of                                                            ##STR41##                                                                     ##STR42##                                                                     ##STR43##                                                                     ##STR44##                                                                     ##STR45##                                                                     ##STR46##                                                                    or                                                                             ##STR47##                                                                    ______________________________________                                        Compound No. L        M        Q                                              ______________________________________                                        5.1          --       H        H                                              5.2          --       H        Me                                             5.3          --       H        Et                                             5.4          --       H        Pr                                             5.5          --       H        i-Pr                                           5.6          --       H        Bu                                             5.7          --       H        t-Bu                                           5.8          --       H        CH.sub.2 CHCH.sub.2                            5.9          --       H        CH.sub.2 C CH                                  5.10         --       H        CH.sub.2 CH.sub.2 Cl                           5.11         --       H        CH.sub.2 CH.sub.2 F                            5.12         --       H        CH.sub.2 CHCHCl                                5.13         --       H        CH.sub.2 OMe                                   5.14         --       H        CH.sub.2 SMe                                   5.15         --       H        CH.sub.2 Ph                                    5.16         --       H        Ph                                             5.17         --       H        COMe                                           5.18         --       H        COPh                                           5.19         --       H        CO.sub.2 Et                                    5.20         --       H        CO.sub.2 t-Bu                                  5.21         --       H        SO.sub.2 Me                                    5.22         --       H        SO.sub.2 Ph                                    5.23         --       Me       Me                                             5.24         --       Me       COMe                                           5.25         --       Me       COPh                                           5.26         --       Me       CO.sub.2 Et                                    5.27         --       Et       Et                                             5.28         --       Et       COMe                                           5.29         --       Et       COPh                                           5.30         (CH.sub.2).sub.2                                                                       H        H                                              5.31         (CH.sub.2).sub.2                                                                       H        Me                                             5.32         (CH.sub.2).sub.2                                                                       H        Et                                             5.33         (CH.sub.2).sub.2                                                                       H        Pr                                             5.34         (CH.sub.2).sub.2                                                                       H        cyc-Pr                                         5.35         (CH.sub.2).sub.2                                                                       H        CH.sub.2 Ph                                    5.36         (CH.sub.2).sub.2                                                                       H        Ph                                             5.37         (CH.sub.2).sub.2                                                                       H        COMe                                           5.38         (CH.sub.2).sub.2                                                                       H        COPh                                           5.39         (CH.sub.2).sub.2                                                                       H        CO.sub.2 Et                                    5.40         (CH.sub.2).sub.2                                                                       H        CO.sub.2 t-Bu                                  5.41         (CH.sub.2).sub.2                                                                       Me       Me                                             5.42         (CH.sub.2).sub.2                                                                       Me       Et                                             5.43         (CH.sub.2).sub.2                                                                       Me       Pr                                             5.44         (CH.sub.2).sub.2                                                                       Me       CH.sub.2 Ph                                    5.45         (CH.sub.2).sub.2                                                                       Me       Ph                                             5.46         (CH.sub.2).sub.2                                                                       Me       COMe                                           5.47         (CH.sub.2).sub.2                                                                       Me       COPh                                           5.48         (CH.sub.2).sub.2                                                                       Me       CO.sub.2 Et                                    5.49         (CH.sub.2).sub.2                                                                       Me       CO.sub.2 t-Bu                                  5.50         (CH.sub.2).sub.2                                                                       Et       Et                                             5.51         (CH.sub.2).sub.2                                                                       Et       Pr                                             5.52         (CH.sub.2).sub.2                                                                       (CH.sub.2).sub.4                                        5.53         (CH.sub.2).sub.2                                                                       (CH.sub.2).sub.5                                        5.54         (CH.sub.2).sub.3                                                                       Me       Me                                             5.55         (CH.sub.2).sub.3                                                                       Me       Et                                             5.56         (CH.sub.2).sub.3                                                                       Me       Pr                                             5.57         (CH.sub.2).sub.3                                                                       Me       CH.sub.2 Ph                                    5.58         (CH.sub.2).sub.3                                                                       Me       Ph                                             5.59         (CH.sub.2).sub.3                                                                       Me       COMe                                           5.60         (CH.sub.2).sub.3                                                                       Me       COPh                                           5.61         (CH.sub.2).sub.3                                                                       Me       CO.sub.2 Et                                    5.63         (CH.sub.2).sub.3                                                                       Me       CO.sub.2 t-Bu                                  5.63         (CH.sub.2).sub.3                                                                       Et       Et                                             5.64         (CH.sub.2).sub.3                                                                       Et       Pr                                             5.65         (CH.sub.2).sub.3                                                                       (CH.sub.2).sub.4                                        5.66         (CH.sub.2).sub.3                                                                       (CH.sub.2).sub.5                                        ______________________________________                                    

                  TABLE 6                                                         ______________________________________                                        In the compounds of                                                            ##STR48##                                                                     ##STR49##                                                                     ##STR50##                                                                     ##STR51##                                                                     ##STR52##                                                                     ##STR53##                                                                    or                                                                             ##STR54##                                                                    ______________________________________                                        Compound No.                                                                              T          U           V                                          ______________________________________                                        6.1         --         Me          NH.sub.2                                   6.2         --         Et          NH.sub.2                                   6.3         --         Pr          NH.sub.2                                   6.4         --         Bu          NH.sub.2                                   6.5         --         t-Bu        NH.sub.2                                   6.6         --         Ph          NH.sub.2                                   6.7         --         (2-Cl)Ph    NH.sub.2                                   6.8         --         (4-Cl)Ph    NH.sub.2                                   6.9         --         (2-F)Ph     NH.sub.2                                   6.10        --         (4-F)Ph     NH.sub.2                                   6.11        --         CH.sub.2 Cl NH.sub.2                                   6.12        --         CH.sub.2 CF.sub.3                                                                         NH.sub.2                                   6.13        --         Me          NHMe                                       6.14        --         Et          NHMe                                       6.15        --         Pr          NHMe                                       6.16        --         Bu          NHMe                                       6.17        --         t-Bu        NHMe                                       6.18        --         Ph          NHMe                                       6.19        --         (2-Cl)Ph    NHMe                                       6.20        --         (4-Cl)Ph    NHMe                                       6.21        --         (2-F)Ph     NHMe                                       6.22        --         (4-F)Ph     NHMe                                       6.23        --         CH.sub.2 CCl.sub.3                                                                        NHMe                                       6.24        --         CH.sub.2 CF.sub.3                                                                         NHMe                                       6.25        --         Me          NMe.sub.2                                  6.26        --         Et          NMe.sub.2                                  6.27        --         Pr          NMe.sub.2                                  6.28        --         Bu          NMe.sub.2                                  6.29        --         t-Bu        NMe.sub.2                                  6.30        --         Ph          NMe.sub.2                                  6.31        --         (2-Cl)Ph    NMe.sub.2                                  6.32        --         (4-Cl)Ph    NMe.sub.2                                  6.33        --         (2-F)Ph     NMe.sub.2                                  6.34        --         (4-F)Ph     NMe.sub.2                                  6.35        --         CH.sub.2 CCl.sub.3                                                                        NMe.sub.2                                  6.36        --         CH.sub.2 CF.sub.3                                                                         NMe.sub.2                                  6.37        (CH.sub.2).sub.2 O                                                                       Me          H                                          6.38        (CH.sub.2).sub.2 O                                                                       Me          Me                                         6.39        (CH.sub.2).sub.2 O                                                                       Me          t-Bu                                       6.40        (CH.sub.2).sub.2 O                                                                       Ph          H                                          6.41        (CH.sub.2).sub.2 O                                                                       Ph          Me                                         ______________________________________                                    

A process for producing the compounds of the present invention isdescribed below. Synthesis of the compound of the formula 1! ##STR55##wherein R¹, R² and R³ have the same meanings as defined above. ##STR56##wherein R¹, R² and R³ have the same meanings as defined above, and Zrepresents a leaving group such as halogen or the like. ##STR57##wherein R¹, R⁴ and R⁵ have the same meanings as defined above. ##STR58##wherein R¹ and R⁵ have the same meanings as defined above. ##STR59##wherein R¹ and R⁵ have the same meanings as defined above.

Synthesis of the compound of the formula 2! ##STR60## wherein X, R² andR⁶ have the same meanings as defined above. ##STR61## wherein X, R² andR⁶ have the same meanings as defined above.

In (Process 1), the compound can be produced by the method reported inBull. Soc. Chim. Fr., p. 293 (1966) and Chem. Ber. vol. 59, p. 1282(1926).

In (Process 2), the compound can be produced by the method reported inChem. Ber., vol. 59, p. 601 (1926) and J. Prak. Chem., vol. 143, p. 259(1935).

In (Process 3), the compound can be produced by the method reported inChemical Abstracts, vol. 40, p. 4056 (1946) and J. Chem. Soc., p. 87(1946).

In (Process 4), the compound can be produced by the method reported inJ. Heterocyclic Chem., vol. 22, p. 1621 (1985).

In (Process 5), the compound can be produced by the method reported inChemical Abstracts, vol. 58, p. 3408 (1963) and Chemical Abstracts, vol.61, p. 8298 (1964).

A method of producing a novel compound of the formula 2! of (Process 6)is described below.

3-Halogeno-1-alkylpyrazole 4! can be produced by diazotizing3-amino-1-alkylpyrazole 3! in a usual manner, and adding a copperhalide.

It is desirable that the diazotization is normally conducted in amineral acid such as hydrochloric acid, sulfuric acid or the like at atemperature of from -10° C. to room temperature, preferably from 0° to10° C. In the reaction with the copper halide, it is possible todirectly add the same to a diazonium solution. However, it is desirableto suspend a copper saltin in an inert solvent such as chloroform or thelike and add a diazonium solution to the suspension. The reaction ispreferably conducted at from 0° to 100° C. or at a reflux temperature ofa solvent.

Then, the 5-position of the resulting compound is lithiolized using alithium compound such as LDA or the like, and the thus-obtained compoundis reacted with carbon dioxide gas or a chloroformic acid ester, makingit possible to form the intended product 2!.

It is usually advisable to conduct the lithiolization and theesterification in an inert solvent such as diethyl ether, THF or thelike at a temperature of from -120° C. to room temperature, preferablyfrom -80° C. to 0° C. After the completion of the reaction, thepost-treatment is conducted in a usual manner to obtain the intendedproduct.

In (Process 7), the intended product 2! can be formed by converting a3-halogeno-1-alkyl-5-pyrazolecarboxylic acid in a usual manner into acarbonyl halide 5!, and then reacting the same with alcohols.

In the conversion into a carbonyl halide, it is possible to directly adda thionyl halide, a phosphorus halide or the like. It is usuallyadvisable to conduct the conversion in an inert solvent such aschloroform, benzene, toluene or the like at from 0° to 120° C. or at areflux temperature of a solvent.

The esterification can usually be conducted using an appropriate inertsolvent. Examples of the solvent include aromatic hydrocarbons such astoluene, xylene, chlorobenzene and the like; halogenated hydrocarbonssuch as dichloroethane and the like; ethers such as diisopropyl ether,dioxane and the like; nitrites such as acetonitrile and the like; andpolar solvents such as dimethylsulfoxide, dimethylformamide and thelike.

An organic base (such as pyridine, triethylamine or the like) or aninorganic base (potassium carbonate, sodium hydroxide or the like) maybe added as required.

With respect to the amount of the reagent used in the reaction, anamount of an alcohol is between 1 and 3 equivalents per equivalent ofthe compound of the formula 5!.

Any reaction temperature can be employed in the above-mentionedreaction. However, it is preferably between 0° C. and 50° C.

The plant diseases to be controlled by the compounds of the presentinvention are as follows.

Rice blast (Pyricularia oryzae), Helminthosporium leaft spot(Cochliobolus miyabeanus) and Sheat blight (Rhizoctonia solani) ofpaddy.

Powdery mildew (Erysiphe graminis f. sp. hordei, f. sp. tritici), Stripe(Pyrenophora graminea), Net blotch (Pyrenophora teres), Scab andfusarium blight (Gibberella zeae), Stripe rust, yellow rust, stem rust,black rust, leaf rust, brown rust and dwarf rust (Puccinia striiformis,P. graminis, P. recondite, P. hordei), Snow blight and snow mold(Typhula sp., Micronectriella nivais), Loose smut (Ustilago tritici, U.nuda), Eyespot (Pseudocercosporella herpotrichoides), Scald and leafblotch (Rhynchosporium secalis), Speckled blotch (Septoria tritici), andGlume blotch (Leptosphaeria nodorum) of barley and wheat,

Melanose (Diaporthe citri), Scab (Elsinoe fawcetti), and Common greenmold and blue mold (Penicillium digitatum, P. italicum) of fruit trees,

Blossom blight (Sclerotinia mali), Canker (Valsa mali), Powdery mildew(Podosphaera leucotricha), Alternaria leaf spot (Alternaria mali) andScab (Venturia inaequalis) of apple,

Scab (Venturia nashicola), Black spot (Alternaria Kikuchiana) and Rust(Gymnosporangium haraeanum) of pear,

Brown rot (Sclerotinia cinerea), Scab (Cladosporium carpophilum), andPhomopsis rot (Phomopsis sp.) of peach,

Downy mildew (Plasmopara viticola), Anthracnose (Elsinoe ampelina), Riperot (Glomerella cingulata), Powdery mildew (Uncinula necator) and Rust(Phakopsora ampelopsidis) of grape,

Anthracnose (Gloeosporium kaki) and Angular leaf spot, and Circular leafspot (Cercospora kaki, Mycosphaerella nawae) of persimmon,

Downy mildew (Pseudoperenospora cubensis), Anthracnose (Colletotrichumlagenarium), Powdery mildew (Sphaerotheca fuliginea), and Gummy stemblight (Mycosphaerella melonis) of melon,

Late blight (Phytophthora infestans), Early blight (Alternaria solani)and Leaf mold (Cladosporium fulvam) of tomato,

Brown spot (Phomopsis vexans) and Powdery mildew (Erysiphecichoracoarum) of egg plant,

Alternaria leaf spot (Alternaria japonica) and white spot(Cerocosporella brassicae) of vegetable of the family Cruciferae,

Rust (Puccinia allii) of welsh onion,

Purple seed stain (Cercospora kikuchii), Sphaceloma scab (Elsinoeglycines) and Black spot (Diaporthe phaseololum) of soybean,

Anthracnose (Colletotrichum lindemuthianum) of kidney bean,

Leaf spot (Mycosphaerella personatum) and Brown leaf spot (Cercosporaarachidicola) of peanut,

Powdery mildew (Erysiphe pisi) of garden pea,

Early blight (Alternaria solani) of potato

Powdery mildew (Sphaerotheca humuli) of strawberry,

Net blister blight (Exobasidium reticulatum) and White scab (Elsinoeleucospila) of tea,

Brown spot (Alternaria longipes), Powdery mildew (Erysiphecichoracearum) and Anthracnose (Colletotrichum tabacum) of tobacco,

Cercospora leaf spot (Cercospora beticola) of sugar beat,

Black spot (Diplocarpon rosae) and Powdery mildew (Sphaerotheca pannosa)of rose,

Leaf spot (Septoria chrysanthemiindici) and Rust (Puccinia horiana) ofchrysanthemum,

Gray mold (Botrytis cinerea) of various kinds of crops, and,

Sclerotinia rot (Sclerotinia sclerotiorum) of various kinds of crops.

When the compound of the present invention is used as an agriculturaland horticultural microbicide, it can generally be mixed with anappropriate carrier. Examples of the carrier include solid carriers suchas clay, talc, bentonite, diatomaceous earth and the like; and liquidcarriers such as water, alcohols (such as methanol, ethanol and thelike), aromatic hydrocarbons (such as benzene, toluene, xylene and thelike), chlorinated hydrocarbons, ethers, ketones, esters (such as ethylacetate and the like), acid amides (such as dimethylformamide and thelike) and the like. An emulsifier, a dispersing agent, a suspendingagent, a penetrating agent, a spreader, a stabilizer and the like can beadded thereto as required. The compound of the present inventipracticaluse to practical use in any form of a liquid preparation, anemulsifiable concentrate, a wettable powder, a dust, a granule, aflowable or the like.

When the compounds of the present invention are used as an agriculturaland horticultural microbicide, it can be applied through foliarapplication, soil treatment, seed disinfection or the like. A generalmethod which is used by those skilled in the art is also available. Thecompounds of the present invention may be applied, as required, incombination with preparations or other herbicides, insecticides,disinfectants, plant growth regulators, synergists and the like at thetime of the application. The dose of the compounds in the presentinvention varies depending on an application place, an application time,an application method, diseases to be treated, cultivation crops and thelike. In general, it is between approximately 0.005 kg and 50 kg perhectare.

Formulation examples of fungicides comprising the compounds of thepresent invention as the active ingredient are mentioned hereiunder,which, however, are not limitative. In the following formulationexamples, "part" or "parts" are by weight.

FORMULATION EXAMPLE 1

Emulsifiable concentrates

    ______________________________________                                        Compound of the invention                                                                             20 parts                                              Xylene                  55 parts                                              Cyclohexanone           20 parts                                              Solpol 2680 (trade name,                                                                              5 parts                                               a mixture of a nonionic                                                       surface-active agent and                                                      an anionic-surface active                                                     agent manufactured by Toho                                                    Chemical Co., Ltd.)                                                           ______________________________________                                    

The above-mentioned components are homogeneously mixed together to forman emulsifiable concentrate. Upon use, the emulsifiable concentrate isdiluted from 50 to 20000 times and applied in an amount of from 0.005kg/ha to 50 kg/ha in terms of the active ingredient.

FORMULATION EXAMPLE 2

Wettable powder

    ______________________________________                                        Compound of the invention                                                                            25 parts                                               Zeeklite PFP (trade name,                                                                            66 parts                                               a mixture of kaolinite and                                                    sericite manufactured by                                                      Zeeklite Mining Industries,                                                   Co., Ltd.)                                                                    Solpol 5039 (trade name,                                                                             4 parts                                                an anionic surface-active                                                     agent manufactured by Toho                                                    Chemical Co., Ltd.)                                                           Carplex #80 (trade name,                                                                             3 parts                                                white carbon manufactured                                                     by Shionogi Pharmaceutical                                                    Co., Ltd.)                                                                    Calcium liginin sulfonate                                                                            2 parts                                                ______________________________________                                    

The above-mentioned components are homogeneously mixed together andground to form a wettable powder. Upon use, the wettable powder isdiluted with from 50 to 20000 times and applied in an amount of from0.005 kg/ha to 50 kg/ha in terms of the active ingredient.

FORMULATION EXAMPLE 3

Dusts

    ______________________________________                                        Compound of the invention                                                                            3 parts                                                Carplex #80 (trade name,                                                                             0.5 part                                               manufactured by Shionogi                                                      Pharmaceutical Co., Ltd.)                                                     Clay                   95 parts                                               Di-isopropyl phosphate 1.5 parts                                              ______________________________________                                    

The above-mentioned components are homogeneously mixed together andground to form a dust. Upon use, the dust is applied in an amount offrom 0.005 kg/ha to 50 kg/ha in terms of the active ingredient.

FORMULATION EXAMPLE 4

Granules

    ______________________________________                                        Compound of the invention                                                                             4 parts                                               Bentonite               55 parts                                              Talc                    40 parts                                              Calcium lignin sulfonate                                                                              1 part                                                ______________________________________                                    

The above-mentioned components are mixed homogeneously together andground, incorporated with a small amount of water and mixed togetherwith stirring. The resulting mixture is granulated by means ofextrusion-granulator and dried to form granules. Upon use, the granulesare applied in an amount of from 0.005 kg/ha to 50 kg/ha in terms of theactive ingredient.

FORMULATION EXAMPLE 5

Flowables

    ______________________________________                                        Compound of the invention                                                                              25 parts                                             Solpol 3358 (trade name, 10 parts                                             a nonionic surface-active                                                     agent manufactured by Toho                                                    Chemical Co., Ltd.)                                                           Runox 1000C (trade name, 0.5 part                                             an anionic surface-active                                                     agent manufactured by Toho                                                    Chemical Co., Ltd.)                                                           1% aqueous solution of Xanthan gum                                                                     20 parts                                             (natural high-molecular compound)                                             Water                    44.5 parts                                           ______________________________________                                    

The above-mentioned components except the active ingredient arehomogeneously melted, and then the compound of the invention is addedthereto and well stirred. The resulting mixture is wet-ground in a sandmill to obtain a flowable. Upon use, the flowable is diluted from 50 to20000 times and applied in an amount of from 0.005 kg/ha to 50 kg/ha interms of the active ingredient.

BEST MODE FOR CARRYING THE INVENTION

The present invention is illustrated specifically by referring to thefollowing Examples. However, the present invention is not limitedthereto.

Synthesis Example 1

Synthesis of 1,3-dimethyl-5-pyrazolecarboxylic acid (Compound No. 1.1 ofthe invention)

2.6 g of ethyl 3-methyl-5-pyrazolecarboxylate was reacted with 2 g ofdimethyl sulfate at from 160° to 170° C. for 2 hours. To this mixturewere added 8.3 g of a 5-N sodium hydroxide solution, and the mixture wasreacted at from 80° to 90° C. for 30 minutes. The reaction mixture wasair-cooled, and acidified with hydrochloric acid to precipitatecrystals. The crystals were collected through filtration, washed withwater, and dried to obtain 1.5 g of the Compound No. 1.1 of the presentinvention.

melting point: from 187° to 189° C.

Synthesis Example 2

Synthesis of 2,4-dimethyl-5-thiazolecarboxylic acid (Compound No. 2.1 ofthe invention)

Twenty grams of thioacetamide and 40 g of methyl 2-chloroacetoacetatewere heat-refluxed in 300 ml of ethanol for 3 hours. The reactionsolution was allowed to cool, and 37 g of potassium carbonate were addedthereto. The resulting mixture was heat-refluxed again for 3 hours.After the completion of the reaction, ethanol was distilled off, and theresidue was extracted with water and with chloroform.

The chloroform layer was dried over anhydrous sodium sulfate, and thesolvent was then distilled off under reduced pressure to obtain 41.9 gof ethyl 2,4-dimethyl-5-thiazolecarboxylate.

After 9.7 g of potassium hydroxide were added to 50 ml of methanol and50 ml of water, 10.2 g of ethyl 2,4-dimethyl-5-thiazolecarboxylate wereadded dropwise thereto at room temperature. The reaction was conductedat room temperature for 1 hour, and the reaction mixture was thenacidified with 2-N hydrochloric acid. After methanol was distilled off,the crystals were collected through filtration, washed with water, anddried to obtain 6.6 g of the Compound No. 2.1 of the present invention.

melting point: from 220° to 225° C.

Synthesis Example 3

Synthesis of ethyl 2-chloro-4-methyl-5-thiazolecarboxylate (Compound No.2.34 of the invention)

25 g of chlorocarbonylsulphenyl chloride was added dropwise to 25 g ofethyl 3-aminocrotonate in 300 ml of toluene while being cooled with ice.The solution was heat-refluxed for 2 hours, and then cooled. Thecrystals precipitated were collected through filtration, and then washedtwice with toluene to obtain 22.3 g of4-methyl-5-ethoxycarbonyl-2-thiazolone as purple crystals.

60 ml of phosphorus oxychloride were added to 22.3 g of4-methyl-5-ethoxycarbonyl-2-thiazolone, and the mixture washeat-refluxed for 16 hours. The reaction solution was cooled, then addedto ice water, and neutralized with potassium carbonate. The resultingmixture was extracted with ethyl acetate, and then dried over anhydroussodium sulfate. The solvent was distilled off under reduced pressure toobtain 19 g of a crude product. This crude product was purified throughsilica-gel column chromatography (chloroform) to obtain 15.7 g of theCompound No. 2.34 of the present invention as white crystals.

melting point: from 37.5° to 39.0° C.

Synthesis Example 4

Synthesis of ethyl 3-chloro-1-methyl-5-pyrazolecarboxylate (Compound No.4.3 (a) of the invention)

6.5 g of 3-amino-1-methylpyrazole was dissolved in 55 ml of conc.hydrochloric acid. To this solution was added dropwise a solution of6.22 g of sodium nitrite in 12.5 ml of water while maintaining thetemperature of from 0° to 5° C. through cooling with ice. After thecompletion of the dropwise addition, the stirring was continued at thistemperature for 1 hour. The above-mentioned diazonium solution was addeddropwise to a suspension of 7 g of cuprous chloride in 55 ml ofchloroform. 2 g of cuprous chloride were twice added thereto during thattime.

After the completion of the dropwise addition, the mixture was reactedat 50° C. for 5 hours, and was then stirred at room temperature for 15hours. This solution was filtered using a Celite, and was thenneutralized with a sodium carbonate aqueous solution. The chloroformlayer was extracted, and the aqueous layer was further extracted twicewith 50 ml of chloroform. The combined chloroform solution was washedwith a saturated aqueous solution of sodium chloride, and was dried overanhydrous sodium sulfate. The solvent was distilled off under reducedpressure to obtain 7 g of a crude product.

This crude product was purified through silica-gel column chromatographyto obtain 5.2 g of 3-chloro-1-methylpyrazole as a yellow oil.

Then, 5 g of this compound were dissolved in 50 ml of tetrahydrofuran,and the solution was cooled to -70° C . To this solution was addeddropwise an LDA solution (prepared from 4.5 g of diisopropylamine and18.8 g of n-butyl lithium (15%)). After the completion of the dropwiseaddition, the mixture was further stirred at -70° C. for 1 hour.

The above-mentioned lithiolized pyrazole solution was added dropwise toa solution of 9.5 g of ethyl chloroformate in 50 ml of tetrahydrofuranat -70° C. After the completion of the dropwise addition, the mixturewas further stirred at the same temperature for 3 hours. The reactionmixture was quenched with 5-% hydrochloric acid, concentrated underreduced pressure, and extracted twice with 80 ml of chloroform. Theorganic layer was dried over anhydrous sodium sulfate, and the solventwas then distilled off under reduced pressure to obtain a crude product.

This crude product was purified through silica-gel column chromatographyto obtain 7.2 g of the Compound No. 4.3 (a) of the present invention.melting point: from 37.5° to 38.5° C.

Synthesis Example 5

Synthesis of 3-chloro-1-methyl-5-pyrazolecarboxylic acid (Compound No.4.1 (a) of the invention)

3.5 g of the Compound No. 4.3 (a) formed in Synthesis Example 4 wasdissolved in 20 ml of ethanol and 20 ml of water, and 1.8 g of sodiumhydroxide were added thereto. The mixture was stirred at roomtemperature for 15 hours, and was neutralized with hydrochloric acid toprecipitate crystals. The crystals were collected through filtration,washed with cold water, and dried to obtain 2.7 g of the Compound No.4.1 (a) of the present invention.

melting point: from 171° to 174° C.

Synthesis Example 6

Synthesis of 3-chloro-1-methyl-5-pyrazolecarbonyl chloride

100 g of 3-chloro-1-methyl-5-pyrazole-carboxylic acid (the Compound No.4.1 (a) of the present invention) were suspended in 200 ml of benzene,and 150 ml of thionyl chloride were added thereto dropwise. Then, themixture was heat-refluxed for 4 hours. The reaction mixture was allowedto cool, and the solvent was then distilled off under reduced pressure.The resulting residue was distilled under reduced pressure to obtain 103g of the intended 3-chloro-1-methyl-5-pyrazolecarbonyl chloride.

boiling point: from 78° to 80° C./2 mmHg.

Synthesis Example 7

Synthesis of benzyl 3-chloro-1-methyl-5-pyrazolecarboxylate (CompoundNo. 3.93 (a) of the invention)

1.6 g of benzyl alcohol was dissolved in 50 ml of chloroform. To thissolution were added dropwise 1.8 g of triethylamine and then 3.0 g of3-chloro-1-methyl-5-pyrazolecarbonyl chloride while maintaining thetemperature of from 0° to 5° C. through cooling with ice. Further, asmall amount of 4-dimethylaminopyridine was added thereto. After thecompletion of the addition, the mixture was stirred at room temperaturefor 3.5 hours. To add this solution were added 50 ml of water. Thechloroform layer was extracted, and dried over anhydrous sodium sulfate.The solvent was distilled off under reduced pressure, and the resultingresidue was purified through silica-gel chromatography (chloroform) toobtain 3.7 g of the compound No. 3.93 (a) of the present invention.

n_(D) ¹⁹.9 1.5564

The physical data of the compound of the formula 2! which was producedby the above-mentioned methods are shown in Table 7. In this, CompoundNo. is the same as that shown in Tables 3 to 6.

                  TABLE 7                                                         ______________________________________                                        Compound No.      Physical data                                               ______________________________________                                        3.1 (a)           m.p. 87-88° C.                                       3.4 (a)           m.p. 52.5-53.5° C.                                   3.27 (a)          m.p. 83-86° C.                                       3.29 (a)          m.p. 132.5-133° C.                                   3.52 (a)          m.p. 165.0-166.0° C.                                 3.93 (a)          n.sub.D.sup.19.9 1.5564                                     3.96 (a)          m.p. 96.0-97.0° C.                                   3.99 (a)          m.p. 31-32° C.                                       3.105 (a)         m.p. 33.5-35.0° C.                                   3.108 (a)         m.p. 68.5-69.5° C.                                   3.109 (a)         m.p. 52-54° C.                                       3.112 (a)         m.p. 45-46° C.                                       3.114 (a)         m.p. 76.5-78° C.                                     3.118 (a)         m.p. 83-84° C.                                       3.119 (a)         m.p. 91.5-93.0° C.                                   3.120 (a)         m.p. 60-62° C.                                       3.121 (a)         m.p. 92-93° C.                                       3.122 (a)         m.p. 101.0-102.5° C.                                 3.123 (a)         m.p. 89-90° C.                                       3.124 (a)         m.p. 131-132° C.                                     3.125 (a)         m.p. 89-91° C.                                       3.129 (a)         m.p. 41-43° C.                                       3.133 (a)         m.p. 96-98° C.                                       3.136 (a)         m.p. 96-97° C.                                       3.140 (a)         m.p. 80.5-83.0° C.                                   3.144 (a)         m.p. 123.0-125.0° C.                                 3.151 (a)         m.p. 70-71° C.                                       3.152 (a)         m.p. 44-46° C.                                       3.154 (a)         m.p. 71.0-72.5° C.                                   3.155 (a)         m.p. 30-32° C.                                       3.156 (a)         m.p. 132-136° C.                                     3.158 (a)         m.p. 40.0-41.5° C.                                   3.161 (a)         m.p. 77-78° C.                                       3.163 (a)         n.sub.D.sup.20.0 1.5830                                     3.166 (a)         m.p. 45-46° C.                                       3.167 (a)         m.p. 35-36° C.                                       3.168 (a)         m.p. 96-97° C.                                       3.170 (a)         n.sub.D.sup.20.8 1.5782                                     3.178 (a)         m.p. 95-96° C.                                       3.184 (a)         m.p. 142.0-143.5° C.                                 3.185 (a)         m.p. 46-48° C.                                       3.191 (a)         m.p. 32-34° C.                                       3.198 (a)         m.p. 49-51° C.                                       3.229 (a)         n.sub.D.sup.20.1 1.5459                                     3.235 (a)         n.sub.D.sup.20.0 1.5306                                     3.242 (a)         n.sub.D.sup.20.1 1.5570                                     3.273 (a)         n.sub.D.sup.20.1 1.5439                                     3.317 (a)         n.sub.D.sup.20.1 1.5444                                     3.482 (a)         n.sub.D.sup.20.1 1.5323                                     3.515 (a)         m.p. 40-42° C.                                       3.647 (a)         m.p. 72-74° C.                                       3.650 (a)         m.p. 55-57° C.                                       3.675 (a)         m.p. 65.5-66.5° C.                                   4.1 (a)           m.p. 165-168° C.                                     4.1 (b)           m.p. 119-120° C.                                     4.1 (f)           m.p. 155-156° C.                                     4.1 (g)           m.p. 118-122° C.                                     4.2 (a)           m.p. 23-25° C.                                       4.3 (a)           m.p. 37.5-38.5° C.                                   4.4 (a)           n.sub.D.sup.20.0 1.4930                                     4.5 (a)           n.sub.D.sup.20.0 1.3944                                     4.6 (a)           n.sub.D.sup.20.0 1.4906                                     4.8 (a)           n.sub.D.sup.20.0 1.4888                                     4.10 (a)          n.sub.D.sup.19.8 1.4885                                     4.13 (a)          n.sub.D.sup.20.0 1.4872                                     4.14 (a)          m.p. 36-38° C.                                       4.16 (a)          m.p. 37.5-38.5° C.                                   4.18 (a)          n.sub.D.sup.19.9 1.5099                                     4.19 (a)          n.sub.D.sup.20.1 1.5054                                     4.20 (a)          n.sub.D.sup.19.9 1.5140                                     4.21 (a)          n.sub.D.sup.20.1 1.5119                                     4.23 (a)          n.sub.D.sup.20.5 1.5104                                     4.24 (a)          n.sub.D.sup.20.5 1.5082                                     4.25 (a)          m.p. 59-62° C.                                       4.26 (a)          m.p. 83-86° C.                                       4.27 (a)          oil                                                         4.31 (a)          n.sub.D.sup.20.0 1.5092                                     4.35 (a)          n.sub.D.sup.20.0 1.5000                                     4.37 (a)          m.p. 35.0-37.5° C.                                   4.41 (a)          n.sub.D.sup.20.1 1.5112                                     4.42 (a)          n.sub.D.sup.20.1 1.5199                                     4.43 (a)          n.sub.D.sup.19.7 1.5367                                     4.44 (a)          n.sub.D.sup.20.1 1.5693                                     4.49 (a)          n.sub.D.sup.19.9 1.5308                                     4.51 (a)          n.sub.D.sup.20.2 1.5028                                     4.52 (a)          n.sub.D.sup.20.0 1.5158                                     4.55 (a)          n.sub.D.sup.20.1 1.5271                                     4.58 (a)          m.p. 50-52° C.                                       4.59 (a)          m.p. 50-52° C.                                       4.61 (a)          n.sub.D.sup.20.1 1.5236                                     4.67 (a)          n.sub.D.sup.20.1 1.5057                                     4.70 (a)          n.sub.D.sup.20.0 1.4743                                     4.73 (a)          m.p. 73-74° C.                                       4.74 (a)          m.p. 49-52° C.                                       4.75 (a)          n.sub.D.sup.20.2 1.5295                                     4.76 (a)          n.sub.D.sup.19.7 1.5172                                     4.77 (a)          n.sub.D.sup.19.8 1.4978                                     4.78 (a)          n.sub.D.sup.19.8 1.5124                                     4.82 (a)          m.p. 41-42° C.                                       4.84 (a)          m.p. 74-76° C.                                       4.85 (a)          m.p. 60-62° C.                                       4.86 (a)          m.p. 72-73° C.                                       4.87 (a)          m.p. 75-76° C.                                       4.88 (a)          n.sub.D.sup.20.1 1.5498                                     4.89 (a)          n.sub.D.sup.20.1 1.5351                                     4.90 (a)          n.sub.D.sup.20.1 1.5245                                     4.91 (a)          n.sub.D.sup.20.1 1.5698                                     4.92 (a)          m.p. 65.5-66.5° C.                                   4.93 (a)          m.p. 88-89° C.                                       4.94 (a)          m.p. 74-75° C.                                       4.96 (a)          n.sub.D.sup.20.1 1.5161                                     4.105 (a)         n.sub.D.sup.20.1 1.4975                                     4.123 (a)         n.sub.D.sup.20.1 1.4924                                     4.126 (a)         n.sub.D.sup.19.8 1.4972                                     4.127 (a)         n.sub.D.sup.19.9 1.4920                                     4.182 (a)         n.sub.D.sup.20.0 1.5412                                     4.194 (a)         m.p. 88-91° C.                                       4.298 (a)         n.sub.D.sup.20.0 1.4964                                     4.457 (a)         n.sub.D.sup.20.1 1.5389                                     4.460 (a)         m.p. 47-49° C.                                       4.490 (a)         m.p. 95.5-96.5° C.                                   5.7 (a)           viscous substance                                           5.18 (a)          m.p. 162-163° C.                                     5.20 (a)          viscous substance                                           5.22 (a)          m.p. 165-167° C.                                     5.23 (a)          viscous substance                                           5.40 (a)          m.p. 51-52.5° C.                                     5.41 (a)          n.sub.D.sup.20.0 1.5002                                     6.1 (a)           m.p. 145-146° C.                                     6.11 (a)          m.p. 156-158° C.                                     6.25 (a)          m.p. 72-73° C.                                       6.38 (a)          m.p. 37-44° C.                                       ______________________________________                                    

The usefulness of the compounds of the present invention is specificallydescribed in the following Test Examples. However, the present inventionis not limited thereto.

Test Example 1

Test for effect of controlling Downy mildew (Pseudoperonospora cubensis)of a cucumber

A chemical solution obtained by diluting the emulsifiable concentrate ofthe compounds of the present invention to 500 ppm with water was sprayedon a cucumber (brand: Sagami Hanjiro) grown to 1.5-leaf stage in a pothaving a diameter of 7 cm at a dose of 20 ml/pot using a spray gun.

The following day, a spore suspension (2 x 105 spores/ml) of a downymildew strain (Pseudoperonospora cubensis) of a cucumber was sprayed tothe cucumber, and the pot was placed overnight in an inoculation boxhaving a temperature of 25° C. and a humidity of 95% or more. Then, thepot was put in a greenhouse. After 7 days of inoculation, a ratio of ainfected and spotted area formed to the leaf inoculated was measured,and a protective value was calculated according to the followingequation.

    ______________________________________                                        Protective value =                                                             1 - (infected and spotted area ratio in treated                              region/infected and spotted area ratio in                                     untreated region)! × 100                                                ______________________________________                                    

As a result, the following compounds of the present invention indicateda protective value of 100.

Compound No. 1.1, No. 2.1, No. 2.32, No. 3.93 (a), No. 3.99 (a), No.3.105 (a), No. 3.133 (a), No. 3.158 (a), No. 3.675 (a), No. 4.1 (a), No.4.1 (g), No. 4.3 (a)

Test Example 2 Test for controlling Rice blast (Pyricularria oryzae) ofpaddy (paddy water application)

10 ml of a chemical solution prepared by diluting the emulsifiableconcentrate of the compounds of the present invention 500 ppm with waterwere drenched to a paddy grown to 1.5-leaf stage in a 1/20000-are beakerpot. After two weeks a conidium suspension of a paddy rice blast strainwas inoculated in the thus-treated paddy through spraying. The paddy wasinfected with the strain at approximately 24° C. and a relative humidityof from 95 to 100% for 24 hours. then, the paddy was left to stand in agreenhouse. After approximately one week, a degree of attack of diseasewas evalulated according to the six scores of from 0 to 5.

(Evaluation standard)

    ______________________________________                                        Infection index  Degree of attack of disease                                  ______________________________________                                        0                no attack                                                    1                lesion number: 1 to 5                                        2                lesion number: 6 to 20                                       3                lesion number: 21 to 40                                      4                lesion number: 41 to 70                                      5                lesion number: 71 or more                                    ______________________________________                                    

As a result, the following compounds of the present invention indicatedan infection index of 1.

Compound No. 1.1, No. 1.3, No. 2.1, No. 2.18, No. 2.32, No. 2.33, No.2.34, No. 2.41, No. 3.27 (a), No. 3.29 (a), No. 3.93 (a), No. 3.99 (a),No. 3.105 (a), No. 3.122 (a), No. 3.125 (a), No. 3.158 (a), No. 3.185(a), No. 3.198 (a), No. 3.229 (a), No. 3.242 (a), No. 3.675 (a), No. 4.1(a), No. 4.3 (a), No. 4.6 (a), No. 4.60 (a), No. 4.61 (a), No. 4.79 (a),No. 4.89 (a), No. 4.83 (a), No. 4.91 (a), No. 4.92 (a), No. 4.94 (a),No. 4.126 (a), No. 4.298 (a), No. 4.460 (a), No. 5.18 (a), No. 5.22 (a),No. 6.38 (a), No. 4.1 (g)

Test Example 3

Test for controlling Rice blast (Pyricularria oryzae) of paddy(application of granules)

An aquatic rice (brand: Nihonbare) was grown to 3- to 4-leaf stage in a1/10000-are pot under submerged culture, and the water surface of thispot was treated with granule containing 4% of an active compound. Aftertwo weeks of treatment, a conidium suspension of a paddy rice blaststrain was inoculated in the thus-treated paddy rice through spraying.The pot was retained at approximately 24° C. and a relative humidity offrom 95 to 100% for 24 hours. Then, this pot was moved to a greenhouse.After 7 days of inoculation, the degree of attack of disease wasevaluated according to the same six scores as in Test Example 2.

The results are shown below.

    ______________________________________                                        Invention    Amount of an active                                                                        Infection                                           Compound     ingredient (g/m.sup.2)                                                                     index                                               ______________________________________                                        No. 1.1      0.24         1                                                   No. 2.1      0.24         1                                                   No. 2.32     0.24         1                                                   No. 4.1 (a)  0.24         1                                                   No. 4.3 (a)  0.24         1                                                   untreated lot                                                                              --           5                                                   ______________________________________                                    

Test Example 4

Test for controlling Rice blast (Pyricularria oryzae) of paddy (seedlingbox treatment)

An aquatic rice (brand: Nihonbare) was cultivated for 25 days using aseedling culture box (30 cm×60 cm×3 cm), and was treated with a dustcontaining 4% of an active compound. The following day, a young seedlingwas transplanted into a 1/10000-are pot, and was grown under submergedculture for 3 weeks. Thereafter, the inoculation and the evaluation wereconducted in the same manner as in Test Example 3.

The results are shown below.

    ______________________________________                                        Invention    Amount of an active                                                                        Infection                                           Compound     ingredient (g/box)                                                                         index                                               ______________________________________                                        No. 1.1      2.4          1                                                   No. 2.1      2.4          1                                                   No. 2.32     2.4          1                                                   No. 4.1 (a)  2.4          1                                                   No. 4.3 (a)  2.4          1                                                   untreated lot                                                                              --           5                                                   ______________________________________                                    

INDUSTRIAL AVAILABILITY

The plant disease control agent of the present invention, the compoundof the present invention and the plant disease control agent containingsaid compound exhibit an excellent agricultural and horticulturalactivity of controlling diseases, and do not damage useful crops.Accordingly, it is useful as an agricultural and horticulturalmicrobicide.

We claim:
 1. Pyrazolecarboxylic acid derivative of the formula 2!:##STR62## wherein X represents a halogen atom,R² represents a C₁ -C₄alkyl group, R⁶ represents a hydrogen atom, an alkali metal atom, analkaline-earth metal atom, ammonium, sulfonium, phosphonium, anoptionally substituted aryl group, an optionally substituted heteroarylgroup, an optionally substituted heterocyclyl group, an optionallysubstituted aryl C₂ -C₄ alkenyl group, -- C(R⁷)(R⁸)!_(m) --R⁹,--N(R¹⁰)(R¹¹) or --N═C(R¹²)(R¹³), R⁷ and R⁸, independently from eachother, represent a hydrogen atom, a halogen atom, a C₁ -C₆ alkyl group(R⁷ and R⁸ may together form a cyclic alkyl group), a C₂ -C₆ alkenylgroup, a C₂ -C₆ alkynyl group, a C₁ -C₆ haloalkyl group, an optionallysubstituted aryl group, an optionally substituted heteroaryl group, a C₁-C₄ alkylcarbonyl group, a C₁ -C₆ alkoxycarbonyl group or a cyano group,m is 0 or 1 to 5, R⁹ represents a hydrogen atom, a halogen atom, a C₁-C₁₀ alkyl group, a C₂ -C₁₀ alkenyl group, a C₂ -C₁₀ alkynyl group, a C₁-C₁₀ haloalkyl group, a C₂ -C₁₀ haloalkenyl group, a C₃ -C₁₀ cycloalkylgroup, an optionally substituted aryl group, an optionally substitutedheteroaryl group, an optionally substituted heterocyclyl group, a C₁ -C₆alkoxy group, a C₁ -C₅ haloalkoxy group, a C₂ -C₆ alkenyloxy group, a C₂-C₆ haloalkenyloxy group, a C₂ -C₆ alkynyloxy group, a C₃ -C₈cycloalkyloxy group, a C₁ -C₆ alkoxy C₁ -C₆ alkyl group, an optionallysubstituted arylalkyloxy group, an optionally substituted aryloxy group,an optionally substituted heteroaryloxy group, a cyano group,--C(O)--R¹⁴, --S(O)_(n) R¹⁵, --N(R¹⁶)(R¹⁷), --ON═C(R¹⁸)(R¹⁹) or OH, R¹⁰and R¹¹, independently from each other, represent a hydrogen atom, a C₁-C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₂ -C₆ alkenyl group, a C₂-C₆ haloalkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₄ alkoxy C₁ -C₄alkyl group, a C₁ -C₄ alkylthio C₁ -C₄ alkyl group, a C₁ -C₆alkylcarbonyl group, a C₁ -C₆ alkoxycarbonyl group, a C₁ -C₆alkylsulfonyl group, an optionally substituted aryl group, an optionallysubstituted arylcarbonyl group or an optionally substituted arylsulfonylgroup, R¹² represents a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group oran optionally substituted aryl group, R¹³ represents an amino group, aC₁ -C₅ monoalkylamino group or a C₁ -C₅ dialkylamino group, R¹⁴represents a hydrogen atom, OH group, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, an optionally substituted aryl group, a C₁ -C₆ alkoxygroup, a C₁ -C₆ haloalkoxy group, a C₂ -C₆ alkenyloxy group, a C₂ -C₆haloalkenyloxy group, a C₂ -C₆ alkynyloxy group or an optionallysubstituted heterocyclyloxy group, n is 0, 1 or 2, R¹⁵ represents ahydrogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group or a C₂-C₆ alkenyl group, R¹⁶ and R¹⁷, independently from each other, representa hydrogen atom, a C₁ -C₆ alkyl group (R¹⁶ and R¹⁷ may together form acyclic alkyl group), a C₃ -C₆ cycloalkyl group, an optionallysubstituted aryl group, an optionally substituted aryl C₂ -C₄ alkylgroup, a C₁ -C₆ alkylcarbonyl group, an optionally substitutedarylcarbonyl group or a C₁ -C₆ alkoxycarbonyl group, R¹⁸ and R¹⁹,independently from each other, represent a hydrogen atom, a C₁ -C₆ alkylgroup or an optionally substituted aryl group, the expression"optionally substituted" means unsubstituted or substituted with from 1to 9 groups selected from a halogen atom, a cyano group, a nitro group,a C₁ -C₄ alkyl group, a C₁ -C₄ alkoxy group, a C₁ -C₄ haloalkyl group, aC₁ -C₄ haloalkoxy group, an aryl group, an aryloxy group, a benzylgroup, a benzyloxy group, a C₃ -C₆ cycloalkyl group, a C₁ -C₄alkoxycarbonyl group, a C₁ -C₄ alkylthio group, a C₁ -C₄ alkylsulfinyl,a C₁ -C₄ alkylsulfonyl group, a styryl group, an amino group, a C₁ -C₄alkoxycarbonylamino group, a C₁ -C₄ alkoxycarbonyloxy group and/or anaminocarbonyl group, the "aryl" group means a residue obtained byremoving one hydrogen atom bound to a carbon atom of an aromatic ringfrom an aromatic hydrocarbon compound, the "heteroaryl" group means aresidue obtained by removing one hydrogen atom bound to a carbon atom ofa heterocyclic ring from a 5-membered or 6-membered aromaticheterocyclic compound, and the "heterocyclyl group" means a residueobtained by removing a hydrogen atom bound to a carbon atom of aheterocyclic ring from a 3- to 6-membered non-aromatic heterocycliccompound.
 2. Pyrazolecarboxylic acid derivatives as claimed in claim 1,wherein X represents a chlorine atom or a bromine atom, and R² is amethyl group.
 3. Pyrazolecarboxylic acid derivatives as claimed in claim1, wherein X represents a chlorine atom or a bromine atom, R² is amethyl group, and R⁶ represents -- C(R⁷)(R⁸)!_(m) --R⁹ (wherein R⁷, R⁸,R⁹ and m have the same meanings as defined above).
 4. Pyrazolecarboxylicacid derivatives as claimed in claim 3, wherein X represents a chlorineatom, R² represents a methyl group, R⁷ and R⁸ represent, independentlyfrom each other, a hydrogen atom, a methyl group or an ethyl group, R⁹is a hydrogen atom, a C₁ -C₁₀ alkyl group or an optionally substitutedaryl group, and m is 0, 1 or
 2. 5. Pyrazolecarboxylic acid derivativesas claimed in claim 1, wherein X represents a chlorine atom, R²represents a methyl group, and R⁶ represents a methyl group, an ethylgroup, a propyl group, a butyl group, a phenyl group, a benzyl group, a2phenylethyl group a 2-phenylpropyl group.
 6. Plant disease controlagent containing as active ingredientone or more pyrazolecarboxylic acidderivatives as claimed in claim 1, 2, 3, 4 or
 5. 7. A plant diseasedescribed in claim 6 is Rice blast (Pyricularia oryzae) of paddy.